Human ILF3 encodes NF90/NF110/NFAR double-stranded RNA-binding proteins with tandem dsRNA-binding domains and a DZF domain that mediates ILF2/NF45 heterodimerization. ILF3 primarily acts as a nuclear and shuttling RNA-binding/ribonucleoprotein factor that recognizes structured dsRNA, including long inverted-repeat-derived duplexes, and modulates RNA processing, translation, circRNA formation, viral RNA biology, and context-specific transcriptional outputs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0003725
double-stranded RNA binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
Reason: ILF3 has tandem dsRNA-binding domains with structural evidence for sequence/structure-sensitive dsRNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0003727
single-stranded RNA binding
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: single-stranded RNA binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0046718
symbiont entry into host cell
|
IEA
GO_REF:0000108 |
REMOVE |
Summary: symbiont entry into host cell is a misannotation: ILF3 viral RNA biology reflects intracellular RNP regulation rather than host-cell entry.
Reason: This electronic inference depends on a virus-receptor interpretation that is not supported; the evidence places ILF3 inside the cell as a dsRNA-binding/RNP factor, not as a host-entry factor or cell-surface virus receptor.
Proposed replacements:
double-stranded RNA binding
Supporting Evidence:
PMID:21123651
Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45 (NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on ribosomes, associate with viral transcripts, and impede viral replication.
file:human/ILF3/ILF3-deep-research-falcon.md
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
|
|
GO:0003677
DNA binding
|
IEA
GO_REF:0000043 |
KEEP AS NON CORE |
Summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the core function.
Reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a context-specific regulatory activity.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
|
|
GO:0003723
RNA binding
|
IEA
GO_REF:0000043 |
KEEP AS NON CORE |
Summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0003725
double-stranded RNA binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
Reason: ILF3 has tandem dsRNA-binding domains with structural evidence for sequence/structure-sensitive dsRNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005730
nucleolus
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: nucleolus is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: cytoplasm is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0051607
defense response to virus
|
IEA
GO_REF:0000043 |
KEEP AS NON CORE |
Summary: defense response to virus is supported as a context-specific viral RNA biology role.
Reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral effects depending on virus and context, so broad viral-defense terms are non-core.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
|
|
GO:0005515
protein binding
|
IPI
PMID:10749851 Protein-arginine methyltransferase I, the predominant protei... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:18337511 NFAR-1 and -2 modulate translation and are required for effi... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:21987769 DRBP76 associates with Ebola virus VP35 and suppresses viral... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:22810585 Viral immune modulators perturb the human molecular network ... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:23853584 The interactomes of influenza virus NS1 and NS2 proteins ide... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:23976881 The HILDA complex coordinates a conditional switch in the 3'... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:39251607 Systematic identification of post-transcriptional regulatory... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0017148
negative regulation of translation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of translation is supported as a context-specific ILF3 RNA fate function.
Reason: ILF3 can promote or repress translation depending on RNA target and cellular context, so this is supported but not the primary molecular function.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0045071
negative regulation of viral genome replication
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of viral genome replication is supported as a context-specific viral RNA biology role.
Reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral effects depending on virus and context, so broad viral-defense terms are non-core.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
|
|
GO:0005654
nucleoplasm
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: nucleoplasm is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005730
nucleolus
|
IDA
GO_REF:0000052 |
KEEP AS NON CORE |
Summary: nucleolus is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005739
mitochondrion
|
IDA
GO_REF:0000052 |
MARK AS OVER ANNOTATED |
Summary: mitochondrion is not supported as an informative ILF3 localization in the current synthesis.
Reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane, or extracellular assignments appear to be high-throughput/context carryover.
Proposed replacements:
nucleus
nucleoplasm
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0160091
spliceosome-depend formation of circular RNA
|
IDA
PMID:28625552 Coordinated circRNA Biogenesis and Function with NF90/NF110 ... |
ACCEPT |
Summary: spliceosome-dependent circular RNA formation is supported as an ILF3/NF90 RNA-processing role.
Reason: ILF3/NF90 influences long dsRNA structures, splicing outcomes, and back-splicing/circRNA formation through structured RNA binding.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
file:human/ILF3/ILF3-deep-research-falcon.md
A mechanistic proposal from this work is that NF45–NF90 can **oligomerize/coating long dsRNA**, creating “beads-on-a-string” assemblies that may **limit ADAR access** and influence splicing outcomes by stabilizing intronic dsRNA structures
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9834807 |
KEEP AS NON CORE |
Summary: cytosol is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9836383 |
KEEP AS NON CORE |
Summary: cytosol is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-9760399 |
ACCEPT |
Summary: nucleoplasm is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-9760402 |
ACCEPT |
Summary: nucleoplasm is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-9760652 |
ACCEPT |
Summary: nucleoplasm is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0001618
virus receptor activity
|
IDA
PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... |
REMOVE |
Summary: virus receptor activity is a misannotation: the cited evidence describes intracellular ILF3/NFAR antiviral RNA regulation rather than virus-entry receptor activity.
Reason: The evidence supports ILF3 as an intracellular dsRNA-binding/RNP factor retained on ribosomes with viral transcripts after PKR-dependent phosphorylation, not as a host-entry factor or cell-surface virus receptor.
Proposed replacements:
double-stranded RNA binding
Supporting Evidence:
PMID:21123651
Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45 (NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on ribosomes, associate with viral transcripts, and impede viral replication.
file:human/ILF3/ILF3-deep-research-falcon.md
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
|
|
GO:0035925
mRNA 3'-UTR AU-rich region binding
|
IDA
PMID:14731398 Facilitation of mRNA deadenylation and decay by the exosome-... |
KEEP AS NON CORE |
Summary: mRNA 3'-UTR AU-rich region binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005515
protein binding
|
IPI
PMID:14731398 Facilitation of mRNA deadenylation and decay by the exosome-... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005576
extracellular region
|
HDA
PMID:27068509 Extracellular matrix remodelling in response to venous hyper... |
MARK AS OVER ANNOTATED |
Summary: extracellular region is not supported as an informative ILF3 localization in the current synthesis.
Reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane, or extracellular assignments appear to be high-throughput/context carryover.
Proposed replacements:
nucleus
nucleoplasm
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005515
protein binding
|
IPI
PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0003725
double-stranded RNA binding
|
IDA
PMID:11777942 Exportin-5, a novel karyopherin, mediates nuclear export of ... |
ACCEPT |
Summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
Reason: ILF3 has tandem dsRNA-binding domains with structural evidence for sequence/structure-sensitive dsRNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:11777942 Exportin-5, a novel karyopherin, mediates nuclear export of ... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005634
nucleus
|
IDA
PMID:8885239 Identification of novel M phase phosphoproteins by expressio... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0016020
membrane
|
HDA
PMID:19946888 Defining the membrane proteome of NK cells. |
MARK AS OVER ANNOTATED |
Summary: membrane is not supported as an informative ILF3 localization in the current synthesis.
Reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane, or extracellular assignments appear to be high-throughput/context carryover.
Proposed replacements:
nucleus
nucleoplasm
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0003723
RNA binding
|
HDA
PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... |
KEEP AS NON CORE |
Summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0003723
RNA binding
|
HDA
PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... |
KEEP AS NON CORE |
Summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005634
nucleus
|
IDA
PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005737
cytoplasm
|
IDA
PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... |
KEEP AS NON CORE |
Summary: cytoplasm is supported as a non-core ILF3 localization.
Reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states, but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0006468
protein phosphorylation
|
IDA
PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... |
REMOVE |
Summary: protein phosphorylation is a misannotation: ILF3/NFAR is phosphorylated by PKR rather than acting as a kinase.
Reason: ILF3 is a dsRNA-binding protein and PKR substrate; the cited paper title states phosphorylation is by PKR, so ILF3 should not be annotated as performing protein phosphorylation.
Supporting Evidence:
PMID:21123651
Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase PKR constitutes a novel mechanism of translational regulation and cellular defense.
|
|
GO:0017148
negative regulation of translation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of translation is supported as a context-specific ILF3 RNA fate function.
Reason: ILF3 can promote or repress translation depending on RNA target and cellular context, so this is supported but not the primary molecular function.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0045071
negative regulation of viral genome replication
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of viral genome replication is supported as a context-specific viral RNA biology role.
Reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral effects depending on virus and context, so broad viral-defense terms are non-core.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
|
|
GO:0005515
protein binding
|
IPI
PMID:17932509 Proteomic and functional analysis of Argonaute-containing mR... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005634
nucleus
|
IDA
PMID:10749851 Protein-arginine methyltransferase I, the predominant protei... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:1990904
ribonucleoprotein complex
|
IDA
PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules. |
ACCEPT |
Summary: ribonucleoprotein complex is consistent with ILF3 function in NF45-NF90/NF110 and mRNP assemblies.
Reason: ILF3 functions through NF45-NF90/NF110 heterodimers and RNA-containing regulatory complexes.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
|
|
GO:0003677
DNA binding
|
IDA
PMID:10574923 Autoantibodies define a family of proteins with conserved do... |
KEEP AS NON CORE |
Summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the core function.
Reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a context-specific regulatory activity.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
|
|
GO:0003677
DNA binding
|
IDA
PMID:7519613 Cloning and expression of cyclosporin A- and FK506-sensitive... |
KEEP AS NON CORE |
Summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the core function.
Reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a context-specific regulatory activity.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
|
|
GO:0003725
double-stranded RNA binding
|
IDA
PMID:10574923 Autoantibodies define a family of proteins with conserved do... |
ACCEPT |
Summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
Reason: ILF3 has tandem dsRNA-binding domains with structural evidence for sequence/structure-sensitive dsRNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:10574923 Autoantibodies define a family of proteins with conserved do... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:11739746 The RNA binding protein nuclear factor 90 functions as both ... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005515
protein binding
|
IPI
PMID:9442054 DNA-dependent protein kinase interacts with antigen receptor... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic for ILF3/NF90 function.
Reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110 ribonucleoprotein complexes, not generic protein binding.
Proposed replacements:
double-stranded RNA binding
ribonucleoprotein complex
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90 (ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)
file:human/ILF3/ILF3-deep-research-falcon.md
**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding
|
|
GO:0005634
nucleus
|
IDA
PMID:11739746 The RNA binding protein nuclear factor 90 functions as both ... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005634
nucleus
|
IDA
PMID:7519613 Cloning and expression of cyclosporin A- and FK506-sensitive... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0045892
negative regulation of DNA-templated transcription
|
IDA
PMID:11739746 The RNA binding protein nuclear factor 90 functions as both ... |
KEEP AS NON CORE |
Summary: negative regulation of DNA-templated transcription is supported as a context-specific transcriptional regulatory role.
Reason: ILF3/NF90 has reported promoter/transcriptional effects, but the current synthesis identifies dsRNA/RNP biology as the core molecular function.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
|
|
GO:0045893
positive regulation of DNA-templated transcription
|
IDA
PMID:11739746 The RNA binding protein nuclear factor 90 functions as both ... |
KEEP AS NON CORE |
Summary: positive regulation of DNA-templated transcription is supported as a context-specific transcriptional regulatory role.
Reason: ILF3/NF90 has reported promoter/transcriptional effects, but the current synthesis identifies dsRNA/RNP biology as the core molecular function.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3 is best understood as a **multifunctional double-stranded RNA-binding protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing → translation), largely through **RNA binding to structured duplex regions** and through formation of a stable **NF45–NF90/NF110 heterodimer**
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
|
|
GO:0003723
RNA binding
|
NAS
PMID:10400669 DRBP76, a double-stranded RNA-binding nuclear protein, is ph... |
KEEP AS NON CORE |
Summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA binding.
Reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but the defining molecular specificity is double-stranded/structured RNA recognition.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
**(c) RNA fate regulation (translation, stability, and small RNA pathways).** Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in **3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress translation and/or influence mRNA stability depending on target/context
file:human/ILF3/ILF3-deep-research-falcon.md
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
|
GO:0005634
nucleus
|
NAS
PMID:10400669 DRBP76, a double-stranded RNA-binding nuclear protein, is ph... |
ACCEPT |
Summary: nucleus is a core ILF3 localization context.
Reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing substrates.
Supporting Evidence:
file:human/ILF3/ILF3-deep-research-falcon.md
ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve **Exportin‑5** in an RNA-dependent fashion
file:human/ILF3/ILF3-deep-research-falcon.md
The literature summarized here corresponds to **human ILF3** encoding **NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with **ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*, 2025-03, https://doi.org/10.1093/nar/gkaf204)
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The literature summarized here corresponds to human ILF3 encoding NF90 and NF110 splice isoforms and matching the UniProt target Q12906 (AlphaFold model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins contain an N‑terminal DZF (domain associated with zinc fingers) followed by two tandem dsRNA-binding domains (dsRBDs/dsRBMs); the DZF domain mediates heterodimerization with ILF2/NF45, the principal binding partner (Winterbourne et al., Nucleic Acids Research, 2025-03, https://doi.org/10.1093/nar/gkaf204) (winterbourne2025integrativestructuralanalysis pages 1-2, winterbourne2025integrativestructuralanalysis pages 3-4). Review literature documents common aliases including NFAR and DRBP76 (Castella et al., WIREs RNA, 2015-03, https://doi.org/10.1002/wrna.1270) (castella2015ilf3andnf90 pages 3-4, castella2015ilf3andnf90 pages 2-3).
ILF3 is best understood as a multifunctional double-stranded RNA-binding protein (dsRBP) that acts across gene expression layers (transcription → RNA processing → translation), largely through RNA binding to structured duplex regions and through formation of a stable NF45–NF90/NF110 heterodimer (grasso2022thepolyvalentrole pages 1-2). ILF3 is not an enzyme catalyzing a chemical reaction; instead, its “primary function” is sequence/structure-sensitive binding to dsRNA and organizing ribonucleoprotein (RNP) complexes that modulate RNA fate (jayachandran2016nuclearfactor90 pages 8-9, castella2015ilf3andnf90 pages 6-8).
(a) dsRNA recognition via tandem dsRBDs. A crystal-structure study shows NF90 (ILF3) uses an ADAR2-like binding mode to recognize dsRNA and can make base-specific contacts in the dsRNA minor groove, supporting the idea that ILF3 binding can be selective for particular duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., Nucleic Acids Research, 2016-12, https://doi.org/10.1093/nar/gkv1508) (jayachandran2016nuclearfactor90 pages 8-9, jayachandran2016nuclearfactor90 pages 12-12).
(b) NF45 (ILF2) heterodimerization as an enabling module. Reviews and structural work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains; NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding (grasso2022thepolyvalentrole pages 2-4, grasso2022thepolyvalentrole pages 1-2).
(c) RNA fate regulation (translation, stability, and small RNA pathways). Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in 3′ UTRs, IRES elements, and pri-miRNA stem regions, and can either promote or repress translation and/or influence mRNA stability depending on target/context (castella2015ilf3andnf90 pages 6-8, grasso2022thepolyvalentrole pages 6-7). A recent review specifically emphasizes roles in miRNA maturation by competition with Microprocessor, and in RISC-mediated silencing through RNA-dependent interactions with AGO2/MOV10 and binding to target mRNAs (Grasso & Kiernan, IJMS, 2022-11, https://doi.org/10.3390/ijms232113584) (grasso2022thepolyvalentrole pages 1-2, grasso2022thepolyvalentrole pages 6-7).
ILF3/NF90/NF110 are primarily nuclear but shuttle between nucleus and cytoplasm in a stimulus- and phosphorylation-dependent manner; export can involve Exportin‑5 in an RNA-dependent fashion (grasso2022thepolyvalentrole pages 1-2). Review evidence also supports nucleolar localization for some isoforms/states and relocalization to the cytoplasm under specific signaling or stress contexts (castella2015ilf3andnf90 pages 2-3).
A recent integrative structural/functional analysis of NF45–NF90 argues that in human cells NF90 cross-links predominantly to Alu elements and that Alu inverted repeats (AluIRs) can form long dsRNA substrates relevant to splicing and editing control (Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204) (winterbourne2025integrativestructuralanalysis pages 1-2). This supports a current understanding in which ILF3 is a major player in the “nuclear dsRNA ecosystem” that determines whether duplex RNAs are edited, processed, or used as regulatory structures.
A mechanistic proposal from this work is that NF45–NF90 can oligomerize/coating long dsRNA, creating “beads-on-a-string” assemblies that may limit ADAR access and influence splicing outcomes by stabilizing intronic dsRNA structures (winterbourne2025integrativestructuralanalysis pages 12-13). The graphical abstract depicting this oligomerization/coating model is shown in (winterbourne2025integrativestructuralanalysis media d1d4ad0d).
A 2023 preprint reports a DZF protein network (ILF2, ILF3, ZFR) that regulates alternative splicing, including mutually exclusive exon (MXE) splicing fidelity, and that ILF3 preferentially binds long dsRNA via its dsRBDs (Haque et al., bioRxiv, 2023-06, https://doi.org/10.1101/2022.06.15.495552) (haque2023anetworkof pages 1-4). This study provides quantitative splicing results (counts/percentages; see Table below) that support ILF3 as part of a definable regulatory module rather than an unstructured “general RBP” (haque2023anetworkof pages 13-16).
Reviews summarize evidence that ILF3/NF90 participates in transcriptional regulation (context-dependent activation or repression at certain promoters) and also directly regulates translation through mRNP assembly and ribosome association, with phosphorylation events influencing compartmentalization and function (castella2015ilf3andnf90 pages 4-5, castella2015ilf3andnf90 pages 6-8).
Foundational literature indicates ILF3/NF90 binds structured viral RNA elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral depending on virus/context, including reported promotion of replication for certain positive-strand RNA viruses (castella2015ilf3andnf90 pages 8-9, castella2015ilf3andnf90 pages 6-8). Structural/biochemical work also highlights ILF3’s dsRNA recognition as a plausible basis for viral RNA interactions (jayachandran2016nuclearfactor90 pages 12-12, jayachandran2016nuclearfactor90 pages 8-9).
A 2024 Molecular Cell review positions dsRNA-binding proteins (dsRBPs) as competitors/co-regulators that shape the fate of dsRNA in cells, explicitly noting NF90 encoded by ILF3 in this landscape (Cottrell et al., Molecular Cell, 2024-01, https://doi.org/10.1016/j.molcel.2023.11.033) (winterbourne2025integrativestructuralanalysis pages 1-2). This type of synthesis is important for current understanding because it links ILF3 to broader systems-level questions: how cells avoid aberrant activation of dsRNA sensors while still using dsRNA structures for normal regulation.
The 2023 DZF-network work suggests dsRNA binding by ILF3 (and ZFR) can be leveraged to modulate splicing fidelity and mutually exclusive exon choices, consistent with the later structural model of dsRNA coating on intronic duplexes (haque2023anetworkof pages 13-16, winterbourne2025integrativestructuralanalysis pages 1-2).
A 2024 review in Signal Transduction and Targeted Therapy describes alternative splicing and RBPs as a major mechanistic axis in development and disease, providing context for why a dsRNA-binding splicing regulator such as ILF3 can have disease relevance even if it is not a spliceosome core factor (Tao et al., 2024-02, https://doi.org/10.1038/s41392-024-01734-2) (tao2024alternativesplicingand pages cited in paper list; no ILF3-specific mechanistic excerpt captured in evidence).
Authoritative reviews summarize multiple cancer-relevant mechanisms (e.g., altered miRNA maturation, mRNA stability of cell-cycle regulators, and chemoresistance axes) and conclude that ILF3/NF90/NF45 components are plausible therapeutic targets or biomarkers in specific contexts (grasso2022thepolyvalentrole pages 10-11, grasso2022thepolyvalentrole pages 2-4). However, the specific evidence snippets retrieved here do not contain cohort-level statistics (hazard ratios, Kaplan–Meier p-values, etc.), so such quantitative biomarker claims cannot be fully substantiated from the current corpus and should be treated as hypotheses pending direct consultation of primary clinical studies (grasso2022thepolyvalentrole pages 10-11).
A foundational review cites that the ILF3 isoform NF110 has been reported as a target of YM155 (a survivin suppressant), illustrating that ILF3-encoded isoforms have appeared in drug-target discussions (castella2015ilf3andnf90 pages 11-12). The excerpt does not include quantitative pharmacology or validation details.
Because ILF3 can promote replication for some viruses by binding viral RNA structures and supporting viral RNP functions, it is conceptually a host-factor target class; conversely, virus-specific roles (pro-viral vs antiviral) indicate that therapeutic targeting would require virus- and context-specific validation (castella2015ilf3andnf90 pages 6-8).
OpenTargets lists ILF3 as associated with cancer with a modest overall score and cites supporting literature (PMIDs 30796096 and 29413056), indicating that curated disease–target evidence exists but is limited in size in that resource snapshot (OpenTargets Search: cancer,hepatocellular carcinoma,glioblastoma,breast cancer,lung cancer-ILF3).
The table below compiles explicit numbers from the retrieved evidence (structural, genomic, and splicing-network datasets).
| Topic | Quantitative detail | Study (first author year) | Publication venue | Experimental context | Notes/interpretation |
|---|---|---|---|---|---|
| Genomic prevalence of Alu elements linked to NF90 binding | Alu elements constitute ~10% of the human genome; ~50% map to introns | Winterbourne 2025 | Nucleic Acids Research | Structural/functional analysis of NF45–NF90 interactions with long nuclear dsRNA and Alu inverted repeats | Supports the idea that ILF3/NF90 is positioned to act broadly on intronic dsRNA formed by repetitive elements (winterbourne2025integrativestructuralanalysis pages 1-2) |
| Length of Alu inverted-repeat dsRNA substrates | Alu inverted repeats can form ~300 bp dsRNA stretches | Winterbourne 2025 | Nucleic Acids Research | Analysis of NF45–NF90 recognition of long dsRNA in human cells | Explains why NF90 is relevant to long endogenous dsRNA substrates affecting splicing/editing (winterbourne2025integrativestructuralanalysis pages 1-2) |
| dsRNA length threshold examined for NF45–NF90 rearrangement | dsRNAs >50 bp were examined | Winterbourne 2025 | Nucleic Acids Research | Domain reorganization/oligomerization studies on long dsRNA | Indicates NF90 complex behavior differs on long dsRNA rather than only short duplexes (winterbourne2025integrativestructuralanalysis pages 1-2) |
| Estimated NF45–NF90 RNA footprint | Continuous RNA-binding surface covers ~26 bp per unit | Winterbourne 2025 | Nucleic Acids Research | Integrative structural model of NF45–NF90 oligomers on dsRNA | Suggests how NF45–NF90 can coat dsRNA and compete with other dsRNA-binding factors such as ADARs (winterbourne2025integrativestructuralanalysis pages 12-13) |
| dsRBD structural similarity to ADAR2 | dsRBD1 r.m.s.d. 1.4 Å over 57 Cα; dsRBD2 r.m.s.d. 1.4 Å over 61 Cα | Jayachandran 2016 | Nucleic Acids Research | Crystal structure comparison of NF90 tandem dsRBDs with ADAR2 | Strong structural evidence that ILF3/NF90 uses an ADAR2-like dsRNA recognition mode (jayachandran2016nuclearfactor90 pages 8-9) |
| Span of dsRNA contacted by NF90/ADAR2-like dsRBDs | ~8–10 base pairs | Jayachandran 2016 | Nucleic Acids Research | Structural/biochemical dsRNA-binding analysis | Indicates local recognition window for NF90 dsRBD-mediated binding within larger duplexes (jayachandran2016nuclearfactor90 pages 8-9) |
| Relative abundance within DZF network | ILF2 and ILF3 are ~one order of magnitude more abundant than ZFR | Haque 2023 | bioRxiv | Transcriptome/protein network analysis of DZF proteins controlling splicing | Suggests ILF2–ILF3 is the dominant DZF complex in many cells (haque2023anetworkof pages 1-4) |
| Number of human DZF genes discussed | 5 DZF genes | Haque 2023 | bioRxiv | Conceptual framework for DZF protein network | Places ILF3 within a small specialized family of pseudoenzyme-like RNA regulators (haque2023anetworkof pages 1-4) |
| Validated mutually exclusive exon (MXE) fidelity events controlled by DZF proteins | Over a dozen validated MXE events | Haque 2023 | bioRxiv | Functional splicing perturbation analysis | Supports a specific role for ILF3 network proteins in splicing fidelity, not just broad RNA binding (haque2023anetworkof pages 1-4) |
| MXE master list size | 810 genes in MXE master list | Haque 2023 | bioRxiv | Splicing analysis pipeline | Defines scale of the candidate event space evaluated (haque2023anetworkof pages 13-16) |
| MXE events passing rMATS cutoffs | 229 events passed cutoffs | Haque 2023 | bioRxiv | Differential splicing analysis | Narrows the high-confidence event set for DZF regulation (haque2023anetworkof pages 13-16) |
| Significant MXE targets of one or more DZF proteins | 22 significant MXE targets | Haque 2023 | bioRxiv | Comparative knockdown analysis of DZF proteins | Shows DZF-dependent regulation is selective rather than universal across MXEs (haque2023anetworkof pages 13-16) |
| Significant MXE targets in ILF3 knockdown | 9 regulated in siILF3 | Haque 2023 | bioRxiv | ILF3 depletion splicing analysis | Direct evidence that ILF3 contributes measurably to MXE control (haque2023anetworkof pages 13-16) |
| Genes represented in at least two MXE datasets | 58 genes | Haque 2023 | bioRxiv | Cross-dataset integration for MXEs | Used to assess reproducibility/overlap of regulated events (haque2023anetworkof pages 13-16) |
| Recurrently significant DZF-regulated MXE genes | 16 of 58 genes (28%) | Haque 2023 | bioRxiv | Integrated MXE analysis | Provides an explicit percentage for recurrent DZF-dependent MXE regulation (haque2023anetworkof pages 13-16) |
| Recurrently significant MXE genes regulated in ILF3 knockdown | 6 genes | Haque 2023 | bioRxiv | Integrated siILF3 splicing analysis | Quantifies ILF3-specific contribution within the DZF network (haque2023anetworkof pages 13-16) |
| EMSA/protein titration range | 0 to 5 µM; points included 0, 0.05, 0.1, 0.2, 0.3, 0.5, 0.75, 1, 2.5, 5 µM | Haque 2023 | bioRxiv | Biochemical RNA-binding assays with ILF-family/DZF complexes | Demonstrates direct concentration-dependent nucleic-acid binding behavior (haque2023anetworkof pages 46-48) |
| RNA substrate sizes used in binding assays | 12mer and 24mer dsRNA; 24mer RNA:DNA hybrids | Haque 2023 | bioRxiv | EMSA-style binding assays | Tests sequence/length dependence and duplex-type specificity of DZF complexes (haque2023anetworkof pages 46-48) |
| Long-dsRNA assembly conditions for NF45–NF90 | 310-bp and 410-bp Cyp1A1 dsRNA; protein:dsRNA ratios 18:1 and 24:1 | Winterbourne 2025 | Nucleic Acids Research | EM/biophysical analysis of oligomerization on long dsRNA | Directly supports the model that NF45–NF90 oligomerizes on long dsRNA substrates (winterbourne2025integrativestructuralanalysis pages 3-4) |
| Mass photometry concentration | Final 37.5 nM | Winterbourne 2025 | Nucleic Acids Research | Mass photometry of NF45–NF90 complexes | Concrete methodological detail for quantitative complex analysis (winterbourne2025integrativestructuralanalysis pages 3-4) |
| SEC-MALS input condition | 100 µL at 0.36 mg/mL | Winterbourne 2025 | Nucleic Acids Research | SEC-MALS characterization of NF45–NF90 | Supports biophysical inference of oligomeric assemblies (winterbourne2025integrativestructuralanalysis pages 3-4) |
| EM sample condition | 4 µL at 10 µg/mL | Winterbourne 2025 | Nucleic Acids Research | Negative-stain EM of protein–RNA complexes | Documents imaging conditions for visualizing NF45–NF90 assemblies (winterbourne2025integrativestructuralanalysis pages 3-4) |
Table: This table compiles explicit numeric findings from the gathered ILF3/NF90/NF110 evidence, spanning structural biology, endogenous dsRNA recognition, and 2023 splicing-network studies. It is useful for quickly locating concrete measurements and dataset sizes that support functional annotation claims.
A coherent current model integrating structural and functional evidence is:
References
(winterbourne2025integrativestructuralanalysis pages 1-2): Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, and Atlanta G Cook. Integrative structural analysis of nf45–nf90 heterodimers reveals architectural rearrangements and oligomerization on binding dsrna. Nucleic Acids Research, Mar 2025. URL: https://doi.org/10.1093/nar/gkaf204, doi:10.1093/nar/gkaf204. This article has 4 citations and is from a highest quality peer-reviewed journal.
(winterbourne2025integrativestructuralanalysis pages 3-4): Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, and Atlanta G Cook. Integrative structural analysis of nf45–nf90 heterodimers reveals architectural rearrangements and oligomerization on binding dsrna. Nucleic Acids Research, Mar 2025. URL: https://doi.org/10.1093/nar/gkaf204, doi:10.1093/nar/gkaf204. This article has 4 citations and is from a highest quality peer-reviewed journal.
(castella2015ilf3andnf90 pages 3-4): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(castella2015ilf3andnf90 pages 2-3): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(grasso2022thepolyvalentrole pages 1-2): Giuseppa Grasso and Rosemary Kiernan. The polyvalent role of nf90 in rna biology. International Journal of Molecular Sciences, 23:13584, Nov 2022. URL: https://doi.org/10.3390/ijms232113584, doi:10.3390/ijms232113584. This article has 9 citations.
(jayachandran2016nuclearfactor90 pages 8-9): Uma Jayachandran, Heather Grey, and Atlanta G. Cook. Nuclear factor 90 uses an adar2-like binding mode to recognize specific bases in dsrna. Nucleic Acids Research, 44:1924-1936, Dec 2016. URL: https://doi.org/10.1093/nar/gkv1508, doi:10.1093/nar/gkv1508. This article has 55 citations and is from a highest quality peer-reviewed journal.
(castella2015ilf3andnf90 pages 6-8): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(jayachandran2016nuclearfactor90 pages 12-12): Uma Jayachandran, Heather Grey, and Atlanta G. Cook. Nuclear factor 90 uses an adar2-like binding mode to recognize specific bases in dsrna. Nucleic Acids Research, 44:1924-1936, Dec 2016. URL: https://doi.org/10.1093/nar/gkv1508, doi:10.1093/nar/gkv1508. This article has 55 citations and is from a highest quality peer-reviewed journal.
(grasso2022thepolyvalentrole pages 2-4): Giuseppa Grasso and Rosemary Kiernan. The polyvalent role of nf90 in rna biology. International Journal of Molecular Sciences, 23:13584, Nov 2022. URL: https://doi.org/10.3390/ijms232113584, doi:10.3390/ijms232113584. This article has 9 citations.
(grasso2022thepolyvalentrole pages 6-7): Giuseppa Grasso and Rosemary Kiernan. The polyvalent role of nf90 in rna biology. International Journal of Molecular Sciences, 23:13584, Nov 2022. URL: https://doi.org/10.3390/ijms232113584, doi:10.3390/ijms232113584. This article has 9 citations.
(winterbourne2025integrativestructuralanalysis pages 12-13): Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, and Atlanta G Cook. Integrative structural analysis of nf45–nf90 heterodimers reveals architectural rearrangements and oligomerization on binding dsrna. Nucleic Acids Research, Mar 2025. URL: https://doi.org/10.1093/nar/gkaf204, doi:10.1093/nar/gkaf204. This article has 4 citations and is from a highest quality peer-reviewed journal.
(winterbourne2025integrativestructuralanalysis media d1d4ad0d): Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, and Atlanta G Cook. Integrative structural analysis of nf45–nf90 heterodimers reveals architectural rearrangements and oligomerization on binding dsrna. Nucleic Acids Research, Mar 2025. URL: https://doi.org/10.1093/nar/gkaf204, doi:10.1093/nar/gkaf204. This article has 4 citations and is from a highest quality peer-reviewed journal.
(haque2023anetworkof pages 1-4): Nazmul Haque, Alexander Will, Atlanta G. Cook, and J. Robert Hogg. A network of dzf proteins controls alternative splicing regulation and fidelity. bioRxiv, Jun 2023. URL: https://doi.org/10.1101/2022.06.15.495552, doi:10.1101/2022.06.15.495552. This article has 14 citations.
(haque2023anetworkof pages 13-16): Nazmul Haque, Alexander Will, Atlanta G. Cook, and J. Robert Hogg. A network of dzf proteins controls alternative splicing regulation and fidelity. bioRxiv, Jun 2023. URL: https://doi.org/10.1101/2022.06.15.495552, doi:10.1101/2022.06.15.495552. This article has 14 citations.
(castella2015ilf3andnf90 pages 4-5): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(castella2015ilf3andnf90 pages 8-9): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(grasso2022thepolyvalentrole pages 10-11): Giuseppa Grasso and Rosemary Kiernan. The polyvalent role of nf90 in rna biology. International Journal of Molecular Sciences, 23:13584, Nov 2022. URL: https://doi.org/10.3390/ijms232113584, doi:10.3390/ijms232113584. This article has 9 citations.
(castella2015ilf3andnf90 pages 11-12): Sandrine Castella, Rozenn Bernard, Mélanie Corno, Aurélie Fradin, and Jean‐Christophe Larcher. Ilf3 and nf90 functions in rna biology. Wiley Interdisciplinary Reviews: RNA, 6:243-256, Mar 2015. URL: https://doi.org/10.1002/wrna.1270, doi:10.1002/wrna.1270. This article has 162 citations.
(OpenTargets Search: cancer,hepatocellular carcinoma,glioblastoma,breast cancer,lung cancer-ILF3): Open Targets Query (cancer,hepatocellular carcinoma,glioblastoma,breast cancer,lung cancer-ILF3, 3 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(haque2023anetworkof pages 46-48): Nazmul Haque, Alexander Will, Atlanta G. Cook, and J. Robert Hogg. A network of dzf proteins controls alternative splicing regulation and fidelity. bioRxiv, Jun 2023. URL: https://doi.org/10.1101/2022.06.15.495552, doi:10.1101/2022.06.15.495552. This article has 14 citations.
id: Q12906
gene_symbol: ILF3
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: 'Human ILF3 encodes NF90/NF110/NFAR double-stranded RNA-binding proteins with tandem dsRNA-binding
domains and a DZF domain that mediates ILF2/NF45 heterodimerization. ILF3 primarily acts as a nuclear
and shuttling RNA-binding/ribonucleoprotein factor that recognizes structured dsRNA, including long
inverted-repeat-derived duplexes, and modulates RNA processing, translation, circRNA formation, viral
RNA biology, and context-specific transcriptional outputs.'
alternative_products:
- name: 1 (NFAR-2, ILF3-E)
id: Q12906-1
- name: 2 (NFAR-1, DRBP76)
id: Q12906-2
sequence_note: VSP_003888, VSP_003889
- name: '3'
id: Q12906-3
sequence_note: VSP_003890, VSP_003891
- name: 4 (DRBP76 Alpha, ILF3-A)
id: Q12906-4
sequence_note: VSP_003883, VSP_003884, VSP_003885
- name: 5 (DRBP76 Delta, Gamma, ILF3-C)
id: Q12906-5
sequence_note: VSP_003886, VSP_003887
- name: '6'
id: Q12906-6
sequence_note: VSP_003883, VSP_003888, VSP_003889
- name: '7'
id: Q12906-7
sequence_note: VSP_003883
existing_annotations:
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
action: ACCEPT
reason: ILF3 has tandem dsRNA-binding domains with structural evidence for
sequence/structure-sensitive dsRNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0003727
label: single-stranded RNA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: single-stranded RNA binding is supported as an RNA-binding activity but is less
specific than dsRNA binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0046718
label: symbiont entry into host cell
evidence_type: IEA
original_reference_id: GO_REF:0000108
review:
summary: 'symbiont entry into host cell is a misannotation: ILF3 viral RNA biology reflects
intracellular RNP regulation rather than host-cell entry.'
action: REMOVE
reason: This electronic inference depends on a virus-receptor interpretation that is not
supported; the evidence places ILF3 inside the cell as a dsRNA-binding/RNP factor, not as a
host-entry factor or cell-surface virus receptor.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
supported_by:
- reference_id: PMID:21123651
supporting_text: Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45
(NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on
ribosomes, associate with viral transcripts, and impede viral replication.
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: Foundational literature indicates ILF3/NF90 binds structured viral RNA
elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral
depending on virus/context, including reported promotion of replication for certain
positive-strand RNA viruses
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- term:
id: GO:0003677
label: DNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the
core function.
action: KEEP_AS_NON_CORE
reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a
context-specific regulatory activity.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- term:
id: GO:0003723
label: RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA
binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
action: ACCEPT
reason: ILF3 has tandem dsRNA-binding domains with structural evidence for
sequence/structure-sensitive dsRNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005730
label: nucleolus
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: nucleolus is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: cytoplasm is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0051607
label: defense response to virus
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: defense response to virus is supported as a context-specific viral RNA biology role.
action: KEEP_AS_NON_CORE
reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral
effects depending on virus and context, so broad viral-defense terms are non-core.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: Foundational literature indicates ILF3/NF90 binds structured viral RNA
elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral
depending on virus/context, including reported promotion of replication for certain
positive-strand RNA viruses
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10749851
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18337511
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21987769
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22810585
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23853584
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23976881
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:39251607
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0017148
label: negative regulation of translation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: negative regulation of translation is supported as a context-specific ILF3 RNA fate
function.
action: KEEP_AS_NON_CORE
reason: ILF3 can promote or repress translation depending on RNA target and cellular context, so
this is supported but not the primary molecular function.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0045071
label: negative regulation of viral genome replication
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: negative regulation of viral genome replication is supported as a context-specific
viral RNA biology role.
action: KEEP_AS_NON_CORE
reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral
effects depending on virus and context, so broad viral-defense terms are non-core.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: Foundational literature indicates ILF3/NF90 binds structured viral RNA
elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral
depending on virus/context, including reported promotion of replication for certain
positive-strand RNA viruses
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: nucleoplasm is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005730
label: nucleolus
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: nucleolus is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005739
label: mitochondrion
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: mitochondrion is not supported as an informative ILF3 localization in the current
synthesis.
action: MARK_AS_OVER_ANNOTATED
reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane,
or extracellular assignments appear to be high-throughput/context carryover.
proposed_replacement_terms:
- id: GO:0005634
label: nucleus
- id: GO:0005654
label: nucleoplasm
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0160091
label: spliceosome-depend formation of circular RNA
evidence_type: IDA
original_reference_id: PMID:28625552
review:
summary: spliceosome-dependent circular RNA formation is supported as an ILF3/NF90
RNA-processing role.
action: ACCEPT
reason: ILF3/NF90 influences long dsRNA structures, splicing outcomes, and back-splicing/circRNA
formation through structured RNA binding.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A mechanistic proposal from this work is that NF45–NF90 can
**oligomerize/coating long dsRNA**, creating “beads-on-a-string” assemblies that may **limit
ADAR access** and influence splicing outcomes by stabilizing intronic dsRNA structures
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9834807
review:
summary: cytosol is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9836383
review:
summary: cytosol is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9760399
review:
summary: nucleoplasm is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9760402
review:
summary: nucleoplasm is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9760652
review:
summary: nucleoplasm is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0001618
label: virus receptor activity
evidence_type: IDA
original_reference_id: PMID:21123651
review:
summary: 'virus receptor activity is a misannotation: the cited evidence describes intracellular
ILF3/NFAR antiviral RNA regulation rather than virus-entry receptor activity.'
action: REMOVE
reason: The evidence supports ILF3 as an intracellular dsRNA-binding/RNP factor retained on
ribosomes with viral transcripts after PKR-dependent phosphorylation, not as a host-entry
factor or cell-surface virus receptor.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
supported_by:
- reference_id: PMID:21123651
supporting_text: Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45
(NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on
ribosomes, associate with viral transcripts, and impede viral replication.
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: Foundational literature indicates ILF3/NF90 binds structured viral RNA
elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral
depending on virus/context, including reported promotion of replication for certain
positive-strand RNA viruses
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- term:
id: GO:0035925
label: mRNA 3'-UTR AU-rich region binding
evidence_type: IDA
original_reference_id: PMID:14731398
review:
summary: mRNA 3'-UTR AU-rich region binding is supported as an RNA-binding activity but is less
specific than dsRNA binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:14731398
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005576
label: extracellular region
evidence_type: HDA
original_reference_id: PMID:27068509
review:
summary: extracellular region is not supported as an informative ILF3 localization in the
current synthesis.
action: MARK_AS_OVER_ANNOTATED
reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane,
or extracellular assignments appear to be high-throughput/context carryover.
proposed_replacement_terms:
- id: GO:0005634
label: nucleus
- id: GO:0005654
label: nucleoplasm
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24965446
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IDA
original_reference_id: PMID:11777942
review:
summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
action: ACCEPT
reason: ILF3 has tandem dsRNA-binding domains with structural evidence for
sequence/structure-sensitive dsRNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11777942
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:8885239
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0016020
label: membrane
evidence_type: HDA
original_reference_id: PMID:19946888
review:
summary: membrane is not supported as an informative ILF3 localization in the current synthesis.
action: MARK_AS_OVER_ANNOTATED
reason: ILF3 is an intracellular nuclear/shuttling RNA-binding protein; mitochondrial, membrane,
or extracellular assignments appear to be high-throughput/context carryover.
proposed_replacement_terms:
- id: GO:0005634
label: nucleus
- id: GO:0005654
label: nucleoplasm
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0003723
label: RNA binding
evidence_type: HDA
original_reference_id: PMID:22658674
review:
summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA
binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0003723
label: RNA binding
evidence_type: HDA
original_reference_id: PMID:22681889
review:
summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA
binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:21123651
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:21123651
review:
summary: cytoplasm is supported as a non-core ILF3 localization.
action: KEEP_AS_NON_CORE
reason: ILF3 shuttles between nucleus and cytoplasm and can occupy nucleolar/cytoplasmic states,
but the strongest mechanistic synthesis emphasizes nuclear dsRNA/RNP roles.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: IDA
original_reference_id: PMID:21123651
review:
summary: 'protein phosphorylation is a misannotation: ILF3/NFAR is phosphorylated by PKR rather than
acting as a kinase.'
action: REMOVE
reason: ILF3 is a dsRNA-binding protein and PKR substrate; the cited paper title states
phosphorylation is by PKR, so ILF3 should not be annotated as performing protein
phosphorylation.
supported_by:
- reference_id: PMID:21123651
supporting_text: Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase
PKR constitutes a novel mechanism of translational regulation and cellular defense.
- term:
id: GO:0017148
label: negative regulation of translation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: negative regulation of translation is supported as a context-specific ILF3 RNA fate
function.
action: KEEP_AS_NON_CORE
reason: ILF3 can promote or repress translation depending on RNA target and cellular context, so
this is supported but not the primary molecular function.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0045071
label: negative regulation of viral genome replication
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: negative regulation of viral genome replication is supported as a context-specific
viral RNA biology role.
action: KEEP_AS_NON_CORE
reason: ILF3/NF90 binds structured viral RNA elements and can have pro-viral or antiviral
effects depending on virus and context, so broad viral-defense terms are non-core.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: Foundational literature indicates ILF3/NF90 binds structured viral RNA
elements (e.g., Flaviviridae UTR structures) and can function either pro-viral or antiviral
depending on virus/context, including reported promotion of replication for certain
positive-strand RNA viruses
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17932509
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:10749851
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:1990904
label: ribonucleoprotein complex
evidence_type: IDA
original_reference_id: PMID:17289661
review:
summary: ribonucleoprotein complex is consistent with ILF3 function in NF45-NF90/NF110 and mRNP
assemblies.
action: ACCEPT
reason: ILF3 functions through NF45-NF90/NF110 heterodimers and RNA-containing regulatory
complexes.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- term:
id: GO:0003677
label: DNA binding
evidence_type: IDA
original_reference_id: PMID:10574923
review:
summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the
core function.
action: KEEP_AS_NON_CORE
reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a
context-specific regulatory activity.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- term:
id: GO:0003677
label: DNA binding
evidence_type: IDA
original_reference_id: PMID:7519613
review:
summary: DNA binding is supported in older NF90/ILF3 transcriptional literature but is not the
core function.
action: KEEP_AS_NON_CORE
reason: The current synthesis centers ILF3 on dsRNA/RNP biology; DNA/promoter binding is a
context-specific regulatory activity.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- term:
id: GO:0003725
label: double-stranded RNA binding
evidence_type: IDA
original_reference_id: PMID:10574923
review:
summary: double-stranded RNA binding is the core ILF3/NF90 molecular function.
action: ACCEPT
reason: ILF3 has tandem dsRNA-binding domains with structural evidence for
sequence/structure-sensitive dsRNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10574923
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11739746
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:9442054
review:
summary: protein binding is too generic for ILF3/NF90 function.
action: MARK_AS_OVER_ANNOTATED
reason: The informative functions are dsRNA binding and assembly of NF45-NF90/NF110
ribonucleoprotein complexes, not generic protein binding.
proposed_replacement_terms:
- id: GO:0003725
label: double-stranded RNA binding
- id: GO:1990904
label: ribonucleoprotein complex
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:11739746
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:7519613
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0045892
label: negative regulation of DNA-templated transcription
evidence_type: IDA
original_reference_id: PMID:11739746
review:
summary: negative regulation of DNA-templated transcription is supported as a context-specific
transcriptional regulatory role.
action: KEEP_AS_NON_CORE
reason: ILF3/NF90 has reported promoter/transcriptional effects, but the current synthesis
identifies dsRNA/RNP biology as the core molecular function.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- term:
id: GO:0045893
label: positive regulation of DNA-templated transcription
evidence_type: IDA
original_reference_id: PMID:11739746
review:
summary: positive regulation of DNA-templated transcription is supported as a context-specific
transcriptional regulatory role.
action: KEEP_AS_NON_CORE
reason: ILF3/NF90 has reported promoter/transcriptional effects, but the current synthesis
identifies dsRNA/RNP biology as the core molecular function.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- term:
id: GO:0003723
label: RNA binding
evidence_type: NAS
original_reference_id: PMID:10400669
review:
summary: RNA binding is supported as an RNA-binding activity but is less specific than dsRNA
binding.
action: KEEP_AS_NON_CORE
reason: ILF3 binds structured RNA elements in 3-prime UTRs and other regulatory contexts, but
the defining molecular specificity is double-stranded/structured RNA recognition.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(c) RNA fate regulation (translation, stability, and small RNA pathways).**
Reviews summarize extensive experimental evidence that ILF3/NF90 binds structured elements in
**3′ UTRs**, **IRES elements**, and **pri-miRNA stem regions**, and can either promote or repress
translation and/or influence mRNA stability depending on target/context'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that
in human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted
repeats (AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- term:
id: GO:0005634
label: nucleus
evidence_type: NAS
original_reference_id: PMID:10400669
review:
summary: nucleus is a core ILF3 localization context.
action: ACCEPT
reason: ILF3/NF90/NF110 are primarily nuclear and act on nuclear dsRNA and transcript-processing
substrates.
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: The literature summarized here corresponds to **human ILF3** encoding
**NF90** and **NF110** splice isoforms and matching the UniProt target **Q12906** (AlphaFold
model AF-Q12906-F1 is explicitly referenced in structural work). ILF3/NF90/NF110 proteins
contain an N‑terminal **DZF (domain associated with zinc fingers)** followed by **two tandem
dsRNA-binding domains (dsRBDs/dsRBMs)**; the DZF domain mediates heterodimerization with
**ILF2/NF45**, the principal binding partner (Winterbourne et al., *Nucleic Acids Research*,
2025-03, https://doi.org/10.1093/nar/gkaf204)
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by
curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
Ensembl Compara
findings: []
- id: GO_REF:0000108
title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10400669
title: DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the
interferon-induced protein kinase, PKR.
findings: []
- id: PMID:10574923
title: Autoantibodies define a family of proteins with conserved double-stranded RNA-binding
domains as well as DNA binding activity.
findings: []
- id: PMID:10749851
title: Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in
cells, interacts with and is regulated by interleukin enhancer-binding factor 3.
findings: []
- id: PMID:11739746
title: The RNA binding protein nuclear factor 90 functions as both a positive and negative
regulator of gene expression in mammalian cells.
findings: []
- id: PMID:11777942
title: Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding
proteins.
findings: []
- id: PMID:14731398
title: Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU.
findings: []
- id: PMID:17289661
title: Molecular composition of IMP1 ribonucleoprotein granules.
findings: []
- id: PMID:17932509
title: Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human
cells.
findings: []
- id: PMID:18337511
title: NFAR-1 and -2 modulate translation and are required for efficient host defense.
findings: []
- id: PMID:19946888
title: Defining the membrane proteome of NK cells.
findings: []
- id: PMID:21123651
title: Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase PKR constitutes
a novel mechanism of translational regulation and cellular defense.
findings: []
- id: PMID:21987769
title: DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.
findings: []
- id: PMID:22658674
title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
findings: []
- id: PMID:22681889
title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
findings: []
- id: PMID:22810585
title: Viral immune modulators perturb the human molecular network by common and unique
strategies.
findings: []
- id: PMID:23853584
title: The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and
provide insights for ADAR1 playing a supportive role in virus replication.
findings: []
- id: PMID:23976881
title: The HILDA complex coordinates a conditional switch in the 3'-untranslated region of the
VEGFA mRNA.
findings: []
- id: PMID:24965446
title: Host factors that interact with the pestivirus N-terminal protease, Npro, are components of
the ribonucleoprotein complex.
findings: []
- id: PMID:27068509
title: 'Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose
veins.'
findings: []
- id: PMID:28625552
title: Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection.
findings: []
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings: []
- id: PMID:39251607
title: Systematic identification of post-transcriptional regulatory modules.
findings: []
- id: PMID:7519613
title: 'Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells:
NF45 and NF90.'
findings: []
- id: PMID:8885239
title: Identification of novel M phase phosphoproteins by expression cloning.
findings: []
- id: PMID:9442054
title: DNA-dependent protein kinase interacts with antigen receptor response element binding
proteins NF90 and NF45.
findings: []
- id: Reactome:R-HSA-9760399
title: ILF3 and HOXC8 bind CDH11 gene promoter
findings: []
- id: Reactome:R-HSA-9760402
title: ILF3 binds HOXC8
findings: []
- id: Reactome:R-HSA-9760652
title: ILF3 binds CDH11 gene promoter
findings: []
- id: Reactome:R-HSA-9834807
title: ILF3 binds PKR
findings: []
- id: Reactome:R-HSA-9836383
title: p-PKR dimer phosphorylates ILF3:ILF2
findings: []
- id: file:human/ILF3/ILF3-deep-research-falcon.md
title: Falcon deep research synthesis for ILF3
findings: []
core_functions:
- description: Sequence- and structure-sensitive double-stranded RNA-binding/RNP factor, usually
acting in NF45-NF90/NF110 complexes, that binds long structured RNAs and regulates RNA
processing, splicing/back-splicing, translation, RNA stability, and viral RNA interactions.
molecular_function:
id: GO:0003725
label: double-stranded RNA binding
directly_involved_in:
- id: GO:0160091
label: spliceosome-depend formation of circular RNA
locations:
- id: GO:0005634
label: nucleus
- id: GO:0005654
label: nucleoplasm
supported_by:
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3 is best understood as a **multifunctional double-stranded RNA-binding
protein (dsRBP)** that acts across gene expression layers (transcription → RNA processing →
translation), largely through **RNA binding to structured duplex regions** and through
formation of a stable **NF45–NF90/NF110 heterodimer**
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(a) dsRNA recognition via tandem dsRBDs.** A crystal-structure study shows NF90
(ILF3) uses an **ADAR2-like binding mode** to recognize dsRNA and can make **base-specific contacts
in the dsRNA minor groove**, supporting the idea that ILF3 binding can be selective for particular
duplex sequence/geometry rather than purely “shape-only” binding (Jayachandran et al., *Nucleic
Acids Research*, 2016-12, https://doi.org/10.1093/nar/gkv1508)'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: '**(b) NF45 (ILF2) heterodimerization as an enabling module.** Reviews and structural
work converge on the model that ILF3/NF90 (and NF110) heterodimerize with NF45 through DZF domains;
NF45 binding stabilizes NF90/NF110 and can enhance or modulate RNA binding'
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: A recent integrative structural/functional analysis of NF45–NF90 argues that in
human cells NF90 cross-links predominantly to **Alu elements** and that **Alu inverted repeats
(AluIRs)** can form long dsRNA substrates relevant to splicing and editing control
(Winterbourne et al., 2025-03, https://doi.org/10.1093/nar/gkaf204)
- reference_id: file:human/ILF3/ILF3-deep-research-falcon.md
supporting_text: ILF3/NF90/NF110 are primarily **nuclear** but **shuttle between nucleus and
cytoplasm** in a stimulus- and phosphorylation-dependent manner; export can involve
**Exportin‑5** in an RNA-dependent fashion
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []