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) |
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