UPF3B (Regulator of nonsense transcripts 3B; also called UPF3X, hUpf3b, RENT3B) is a core factor of the nonsense-mediated mRNA decay (NMD) pathway, the surveillance mechanism that degrades mRNAs bearing premature termination codons. UPF3B is a peripheral component of the exon-junction complex (EJC) that is deposited upstream of exon-exon junctions after splicing. It acts as a molecular adaptor that bridges the EJC core to the central NMD machinery, binding the EJC (through its C-terminal region that contacts EIF4A3 and the MAGOH-RBM8A heterodimer) and recruiting UPF2, which in turn links to the RNA helicase/ATPase UPF1 at the terminating ribosome; together UPF2 and UPF3B stimulate the ATPase and helicase activities of UPF1 to activate NMD. UPF3B binds spliced mRNA upstream of exon-exon junctions, shuttles between nucleus and cytoplasm, and can also stimulate translation in vitro. The gene is X-linked, and loss-of-function mutations cause X-linked syndromic and non-syndromic intellectual disability (including Lujan-Fryns syndrome), reflecting an important role of NMD in neurodevelopment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: UPF3B shuttles between nucleus and cytoplasm and acts in cytoplasmic NMD at the terminating ribosome. Reason: Cytoplasmic activity is consistent with UPF3B's role in cytoplasmic NMD; it shuttles between compartments. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Shuttling between the nucleus and the cytoplasm |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: UPF3B binds spliced mRNA upstream of exon-exon junctions; mRNA binding is a core molecular activity supporting its EJC-associated adaptor role. Reason: Direct mRNA binding is documented and integral to UPF3B's function on spliced transcripts. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Binds spliced mRNA upstream of exon-exon junctions |
| GO:0045727 positive regulation of translation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: In vitro, UPF3B stimulates translation independently of UPF2 and the EJC core. Reason: A documented in vitro activity, but secondary to UPF3B's core NMD/adaptor role; the in vivo significance is less established. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt In vitro, stimulates translation |
| GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | IEA GO_REF:0000002 | ACCEPT | Summary: NMD is the core biological process of UPF3B; this electronic annotation is strongly corroborated by direct experimental evidence. Reason: UPF3B is a core NMD factor; this is its central process. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: A generic nucleic-acid-binding term; UPF3B's relevant activity is the more specific mRNA/RNA binding. Reason: Uninformative parent term; the specific and supported activity is mRNA binding (GO:0003729). Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Binds spliced mRNA upstream of exon-exon junctions |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: UPF3B localizes to the nucleus, where it associates with the EJC after splicing. Reason: Nuclear localization is well documented and integral to EJC loading. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization, consistent with UPF3B shuttling and cytoplasmic NMD. Reason: Correct localization; corroborated by experimental evidence. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0035145 exon-exon junction complex | IEA GO_REF:0000117 | ACCEPT | Summary: UPF3B is a peripheral component of the EJC, a core aspect of its function. Reason: UPF3B associates with the EJC core; well supported electronically and experimentally. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Core component of the mRNA splicing-dependent exon junction complex |
| GO:0045727 positive regulation of translation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic annotation of translation stimulation, also shown in vitro. Reason: Secondary in vitro activity; non-core relative to NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt In vitro, stimulates translation |
| GO:0005515 protein binding | IPI PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | KEEP AS NON CORE | Summary: Interaction with UPF1 and UPF2 (founding NMD-targeting study). Bare protein binding is uninformative; the informative function is the UPF2-EJC bridging adaptor role. Reason: Real, functionally central interactions (UPF1, UPF2) but the generic term is uninformative; the core MF is the molecular adaptor activity. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Recruits UPF2 at the cytoplasmic side of the nuclear envelope |
| GO:0005515 protein binding | IPI PMID:11546873 Role of the nonsense-mediated decay factor hUpf3 in the spli... | KEEP AS NON CORE | Summary: Interaction with RBM8A/Y14 and association with the EJC. Bare term uninformative. Reason: Real EJC-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546873 |
| GO:0005515 protein binding | IPI PMID:11546874 Communication of the position of exon-exon junctions to the ... | KEEP AS NON CORE | Summary: EJC-association study interaction. Bare term uninformative. Reason: Real EJC-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546874 |
| GO:0005515 protein binding | IPI PMID:12417715 Identification of a human decapping complex associated with ... | KEEP AS NON CORE | Summary: Interaction within a decapping complex associated with hUpf proteins. Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:12417715 |
| GO:0005515 protein binding | IPI PMID:15231747 A protein interaction framework for human mRNA degradation. | KEEP AS NON CORE | Summary: mRNA-degradation interaction-framework study. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15231747 |
| GO:0005515 protein binding | IPI PMID:15361857 eIF4G is required for the pioneer round of translation in ma... | KEEP AS NON CORE | Summary: Pioneer-round-of-translation study interaction. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15361857 |
| GO:0005515 protein binding | IPI PMID:15680326 Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so ... | KEEP AS NON CORE | Summary: Staufen1/UPF1 study interaction. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15680326 |
| GO:0005515 protein binding | IPI PMID:16209946 Exon-junction complex components specify distinct routes of ... | KEEP AS NON CORE | Summary: Interaction in study of EJC-dependent NMD routes (UPF2/RNPS1). Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16209946 |
| GO:0005515 protein binding | IPI PMID:16452507 Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to th... | KEEP AS NON CORE | Summary: SURF/EJC complex study interaction. Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16452507 |
| GO:0005515 protein binding | IPI PMID:16601204 Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... | KEEP AS NON CORE | Summary: Interaction in study of hUpf3a/hUpf3b in NMD and translation. Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16601204 |
| GO:0005515 protein binding | IPI PMID:19410547 Disassembly of exon junction complexes by PYM. | KEEP AS NON CORE | Summary: EJC-disassembly (PYM) study interaction. Bare term uninformative. Reason: Real EJC-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19410547 |
| GO:0005515 protein binding | IPI PMID:19417104 SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, re... | KEEP AS NON CORE | Summary: SMG-1 complex (SMG-8/SMG-9) study interaction. Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19417104 |
| GO:0005515 protein binding | IPI PMID:19478851 The hierarchy of exon-junction complex assembly by the splic... | KEEP AS NON CORE | Summary: EJC-assembly-hierarchy study interaction. Bare term uninformative. Reason: Real EJC-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19478851 |
| GO:0005515 protein binding | IPI PMID:19503078 A UPF3-mediated regulatory switch that maintains RNA surveil... | KEEP AS NON CORE | Summary: UPF3-mediated RNA-surveillance switch study interaction. Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19503078 |
| GO:0005515 protein binding | IPI PMID:23084401 The cellular EJC interactome reveals higher-order mRNP struc... | KEEP AS NON CORE | Summary: Cellular EJC interactome study interaction. Bare term uninformative. Reason: Real EJC-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23084401 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Quantitative interactome study interaction. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:26496610 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell endogenous-tagging interactome study interaction. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body localization inferred from the ortholog; relevant to UPF3B's role in neurodevelopment. Reason: Electronically inferred localization; peripheral to the core NMD function. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0043025 neuronal cell body cellular_component |
| GO:0071025 RNA surveillance | NAS PMID:31131562 Nonsense-mediated mRNA decay: The challenge of telling right... | KEEP AS NON CORE | Summary: UPF3B functions in RNA surveillance (NMD is the principal surveillance pathway it serves). Reason: A correct but more general process term; the specific core process is nonsense-mediated decay. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt serving as link between the EJC core and NMD machinery |
| GO:0170010 nonsense-mediated decay complex | NAS PMID:35640974 Structures of nonsense-mediated mRNA decay factors UPF3B and... | ACCEPT | Summary: UPF3B is part of the NMD complex (UPF1-UPF2-UPF3 surveillance complex). Reason: UPF3B is a defined component of the NMD/UPF surveillance complex. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt formation of an UPF1-UPF2-UPF3 surveillance complex |
| GO:2000624 positive regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | NAS PMID:31131562 Nonsense-mediated mRNA decay: The challenge of telling right... | ACCEPT | Summary: UPF3B positively regulates/activates NMD by bridging the EJC to UPF1/UPF2. Reason: UPF3B is an activator of NMD; this regulatory term accurately reflects its role. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt is believed to activate NMD |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Direct (HPA) nucleoplasmic localization. Reason: IDA-supported nuclear localization consistent with EJC loading. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Direct (HPA) nucleolar localization; a secondary localization of uncertain functional relevance to NMD. Reason: Documented IDA localization but peripheral to the core cytoplasmic/nuclear NMD function. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005730 nucleolus cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct (HPA) cytosolic localization, consistent with cytoplasmic NMD. Reason: IDA-supported cytosolic localization consistent with site of action. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005634 nucleus | EXP PMID:11113196 Identification and characterization of human orthologues to ... | ACCEPT | Summary: Experimental nuclear localization. Reason: Direct evidence for nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0003729 mRNA binding | IDA PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | ACCEPT | Summary: Direct demonstration of UPF3B mRNA binding. Reason: Direct support for the core mRNA-binding molecular function. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Binds spliced mRNA upstream of exon-exon junctions |
| GO:0005515 protein binding | IPI PMID:25220460 The RNA helicase DHX34 activates NMD by promoting a transiti... | KEEP AS NON CORE | Summary: Interaction with DHX34 (NMD-activating helicase). Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25220460 |
| GO:0035145 exon-exon junction complex | IDA PMID:11546873 Role of the nonsense-mediated decay factor hUpf3 in the spli... | ACCEPT | Summary: Direct demonstration that UPF3B associates with the EJC. Reason: Direct evidence for EJC membership. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Core component of the mRNA splicing-dependent exon junction complex |
| GO:0035145 exon-exon junction complex | IDA PMID:12718880 Y14 and hUpf3b form an NMD-activating complex. | ACCEPT | Summary: UPF3B and Y14/RBM8A form an NMD-activating complex within the EJC context. Reason: Direct evidence for EJC membership. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Core component of the mRNA splicing-dependent exon junction complex |
| GO:0005515 protein binding | IPI PMID:19864460 Mammalian pre-mRNA 3' end processing factor CF I m 68 functi... | KEEP AS NON CORE | Summary: Interaction with CPSF6. Bare term uninformative. Reason: Real interaction record; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19864460 |
| GO:0005515 protein binding | IPI PMID:23788676 The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of... | KEEP AS NON CORE | Summary: Interaction with the RNA helicase DDX5/p68 that enhances NMD. Bare term uninformative. Reason: Real NMD-relevant interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23788676 |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: High-throughput identification of UPF3B as an mRNA-binding protein. Reason: A more general term than the specific mRNA binding; corroborates the RNA-binding activity. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22658674 |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: High-throughput identification of UPF3B in the mRNA-bound proteome. Reason: General term corroborating RNA-binding activity; the specific term is mRNA binding. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889 |
| GO:0005515 protein binding | IPI PMID:20930030 SMG6 interacts with the exon junction complex via two conser... | KEEP AS NON CORE | Summary: Interaction with SMG6 (EJC-binding NMD factor). Bare term uninformative. Reason: Real NMD-pathway interaction; non-core under generic term. Supporting Evidence: file:human/UPF3B/UPF3B-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20930030 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-159101 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75096 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75097 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8849157 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770131 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770141 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770236 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770847 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9794542 | ACCEPT | Summary: Reactome-curated nucleoplasmic localization. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75097 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75098 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927813 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927832 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927836 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927889 | ACCEPT | Summary: Reactome-curated cytosolic localization. Reason: Consistent with cytoplasmic NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
| GO:0035145 exon-exon junction complex | IDA PMID:16601204 Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... | ACCEPT | Summary: UPF3B associates with the EJC core (hUpf3b NMD/translation study). Reason: Direct evidence for EJC membership. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Core component of the mRNA splicing-dependent exon junction complex |
| GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | IDA PMID:16601204 Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... | ACCEPT | Summary: Direct evidence that UPF3B functions in NMD. Reason: Direct support for the core NMD process. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons |
| GO:0045727 positive regulation of translation | IDA PMID:16601204 Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... | KEEP AS NON CORE | Summary: UPF3B stimulates translation in vitro, independently of UPF2 and the EJC core. Reason: Documented in vitro activity; non-core relative to NMD. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt In vitro, stimulates translation |
| GO:0003729 mRNA binding | IDA PMID:11546873 Role of the nonsense-mediated decay factor hUpf3 in the spli... | ACCEPT | Summary: Direct demonstration of UPF3B RNA/mRNA binding within the post-splicing mRNP. Reason: Direct support for the core mRNA-binding molecular function. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Binds spliced mRNA upstream of exon-exon junctions |
| GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | IMP PMID:18369367 NMD resulting from encephalomyocarditis virus IRES-directed ... | ACCEPT | Summary: Functional (knockdown) evidence that UPF3B is required for NMD. Reason: Functional support for the core NMD process. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons |
| GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | NAS PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | ACCEPT | Summary: UPF3B functions in NMD of premature-stop-codon-containing mRNAs (founding study). Reason: Supports the core NMD process. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons |
| GO:0005634 nucleus | NAS PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | ACCEPT | Summary: Nuclear localization asserted in the founding study. Reason: Consistent with documented nuclear localization. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Nucleus |
| GO:0005737 cytoplasm | NAS PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | ACCEPT | Summary: Cytoplasmic localization asserted in the founding study. Reason: Consistent with cytoplasmic NMD and shuttling. Supporting Evidence: file:human/UPF3B/UPF3B-uniprot.txt Cytoplasm |
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Download this section (compressed HTML)Q: How do UPF3B and its paralog UPF3A differ functionally - is UPF3A an antagonist/buffer of UPF3B-dependent NMD, and how does this balance affect neurodevelopment?
Q: Which neuronal transcripts are the key physiological NMD substrates whose dysregulation underlies UPF3B-associated intellectual disability?
Experiment: Reconstitute the EJC-UPF3B-UPF2-UPF1 assembly in vitro with purified components to quantify how UPF3B (and disease mutants such as Y160D) contribute to UPF1 ATPase/helicase stimulation.
Experiment: Transcriptome-wide NMD-substrate profiling (e.g. RNA-seq with UPF3B knockdown/rescue) in neuronal models to define the UPF3B-dependent NMD regulon and its disease relevance.
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