ELAVL1 encodes HuR, a ubiquitous ELAV-family RNA-binding protein with three RNA recognition motifs. HuR binds preferentially to U-rich and AU-rich elements in mRNA 3-prime untranslated regions, assembles regulatory messenger ribonucleoproteins, and commonly stabilizes bound transcripts or promotes their translation. The protein shuttles between nucleus and cytoplasm; stimulus-dependent phosphorylation and partner interactions regulate this trafficking and thereby tune post-transcriptional expression of stress-response, inflammatory, proliferative, and differentiation genes. HuR can also oppose miRNA-mediated repression at selected targets, while its many organismal phenotypes reflect the identities of the transcripts regulated in each cell context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA evidence from GO_REF:0000033 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. Supporting Evidence: file:human/ELAVL1/ELAVL1-deep-research-manual.md Its defining molecular activity is recognition of AU- and U-rich elements in mRNA 3-prime UTRs. |
| GO:0140517 protein-RNA adaptor activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA evidence from GO_REF:0000033 associates ELAVL1 with protein-RNA adaptor activity. Reason: The phylogenetic inference is consistent with ELAV-family conservation and with HuR coordinating proteins at bound regulatory RNAs. Direct human evidence establishes target-RNA binding and regulatory outcomes, but does not yet demonstrate bridging a defined protein-RNA pair, so this is retained as a contextual family-level activity rather than a core molecular function. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IBA GO_REF:0000033 | ACCEPT | Summary: IBA evidence from GO_REF:0000033 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:0000932 P-body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000044 associates ELAVL1 with P-body. Reason: The UniProt location mapping is plausible and consistent with an RNA-regulatory protein, but P-body localization is conditional and not the principal site of HuR's core activity. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: IEA evidence from GO_REF:0000002 associates ELAVL1 with nucleic acid binding. Reason: The nucleic acid binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | MODIFY | Summary: IEA evidence from GO_REF:0000002 associates ELAVL1 with RNA binding. Reason: The RNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with nucleus. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with cytoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0010494 cytoplasmic stress granule | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with cytoplasmic stress granule. Reason: Stress-granule localization is compatible with regulated HuR ribonucleoprotein trafficking and is supported by orthology, but it is conditional rather than the defining steady-state site of action. |
| GO:0043488 regulation of mRNA stability | IEA GO_REF:0000117 | MODIFY | Summary: IEA evidence from GO_REF:0000117 associates ELAVL1 with regulation of mRNA stability. Reason: ELAVL1 can have target- and partner-dependent effects, but the dominant directly demonstrated activity is stabilization of bound mRNAs; the more specific directional process is preferable here. Proposed replacements: mRNA stabilization |
| GO:1990904 ribonucleoprotein complex | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with ribonucleoprotein complex. Reason: ELAVL1 demonstrably occupies multiple mRNPs, but this very broad complex term does not identify a stable obligate complex or a distinct core function. |
| GO:0005515 protein binding | IPI PMID:19322201 Ubiquitin-mediated proteolysis of HuR by heat shock. | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:19322201 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:19322201 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:25416956 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:25416956 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:25959826 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:25959826 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:32814053 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:32814053 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0000512 lncRNA-mediated post-transcriptional gene silencing | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with lncRNA-mediated post-transcriptional gene silencing. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0003729 mRNA binding | IEA GO_REF:0000120 | MODIFY | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with mRNA binding. Reason: The mRNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0003730 mRNA 3'-UTR binding | IEA GO_REF:0000120 | MODIFY | Summary: IEA evidence from GO_REF:0000120 associates ELAVL1 with mRNA 3'-UTR binding. Reason: The mRNA 3'-UTR binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | REMOVE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with endoplasmic reticulum. Reason: ELAVL1 is a soluble nucleocytoplasmic shuttling RRM protein without a signal peptide or transmembrane segment. No direct human evidence for functional ER membership was found, so this automated orthology transfer is unsupported. |
| GO:0006606 protein import into nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with protein import into nucleus. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0008283 cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with cell population proliferation. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0009749 response to glucose | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with response to glucose. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0010508 positive regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with positive regulation of autophagy. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0016441 post-transcriptional gene silencing | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with post-transcriptional gene silencing. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with protein kinase binding. Reason: Regulated association with kinases is supported and controls HuR phosphorylation/shuttling, but kinase binding is regulatory and context-dependent rather than the core RNA-recognition activity. |
| GO:0032930 positive regulation of superoxide anion generation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with positive regulation of superoxide anion generation. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA evidence from GO_REF:0000107 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0045772 positive regulation of autophagosome size | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with positive regulation of autophagosome size. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0048255 mRNA stabilization | IEA GO_REF:0000107 | ACCEPT | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with mRNA stabilization. Reason: Direct binding, decay-chase, depletion, reporter, and recruitment experiments across multiple target transcripts establish mRNA stabilization as a core ELAVL1 process. |
| GO:0061157 mRNA destabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with mRNA destabilization. Reason: The orthology transfer is retained because HuR effects can be transcript- and partner-dependent, but destabilization is not the dominant human biochemical function and is excluded from the core synthesis. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IEA GO_REF:0000107 | ACCEPT | Summary: IEA evidence from GO_REF:0000107 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:2000036 regulation of stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA evidence from GO_REF:0000107 associates ELAVL1 with regulation of stem cell population maintenance. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA evidence from GO_REF:0000052 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: IDA evidence from GO_REF:0000052 associates ELAVL1 with nucleolus. Reason: The HPA immunofluorescence observation is retained as a context-dependent subnuclear localization, but nucleolar residence is not required for the canonical AU-rich-mRNA stabilization mechanism. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: IDA evidence from GO_REF:0000052 associates ELAVL1 with cytosol. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005634 nucleus | EXP PMID:17632515 Identification and mechanistic characterization of low-molec... | ACCEPT | Summary: EXP evidence from PMID:17632515 associates ELAVL1 with nucleus. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005634 nucleus | EXP PMID:18285462 Posttranslational modification of the AU-rich element bindin... | ACCEPT | Summary: EXP evidence from PMID:18285462 associates ELAVL1 with nucleus. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005737 cytoplasm | EXP PMID:17632515 Identification and mechanistic characterization of low-molec... | ACCEPT | Summary: EXP evidence from PMID:17632515 associates ELAVL1 with cytoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005737 cytoplasm | EXP PMID:18285462 Posttranslational modification of the AU-rich element bindin... | ACCEPT | Summary: EXP evidence from PMID:18285462 associates ELAVL1 with cytoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005515 protein binding | IPI PMID:31358969 5-methylcytosine promotes pathogenesis of bladder cancer thr... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:31358969 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:31358969 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0048255 mRNA stabilization | IDA PMID:31358969 5-methylcytosine promotes pathogenesis of bladder cancer thr... | ACCEPT | Summary: IDA evidence from PMID:31358969 associates ELAVL1 with mRNA stabilization. Reason: Direct binding, decay-chase, depletion, reporter, and recruitment experiments across multiple target transcripts establish mRNA stabilization as a core ELAVL1 process. |
| GO:0005515 protein binding | IPI PMID:27974568 IRAV (FLJ11286), an Interferon-Stimulated Gene with Antivira... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:27974568 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:27974568 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:14731398 Facilitation of mRNA deadenylation and decay by the exosome-... | ACCEPT | Summary: IDA evidence from PMID:14731398 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0005515 protein binding | IPI PMID:18191643 Novel tyrosine phosphorylated and cardiolipin-binding protei... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:18191643 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:18191643 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0005515 protein binding | IPI PMID:27616329 Antagonizing effect of CLPABP on the function of HuR as a re... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:27616329 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:27616329 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0010494 cytoplasmic stress granule | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS evidence from GO_REF:0000024 associates ELAVL1 with cytoplasmic stress granule. Reason: Stress-granule localization is compatible with regulated HuR ribonucleoprotein trafficking and is supported by orthology, but it is conditional rather than the defining steady-state site of action. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IDA PMID:29180010 Role of N-myristoylation in stability and subcellular locali... | ACCEPT | Summary: IDA evidence from PMID:29180010 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:0005515 protein binding | IPI PMID:26489465 Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart D... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:26489465 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:26489465 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:26489465 Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart D... | ACCEPT | Summary: IDA evidence from PMID:26489465 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IDA PMID:26489465 Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart D... | ACCEPT | Summary: IDA evidence from PMID:26489465 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:0005515 protein binding | IPI PMID:14731398 Facilitation of mRNA deadenylation and decay by the exosome-... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:14731398 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:14731398 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0003730 mRNA 3'-UTR binding | IDA PMID:26595526 ERK8 is a novel HuR kinase that regulates tumour suppressor ... | MODIFY | Summary: IDA evidence from PMID:26595526 associates ELAVL1 with mRNA 3'-UTR binding. Reason: The mRNA 3'-UTR binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0035198 miRNA binding | IDA PMID:26595526 ERK8 is a novel HuR kinase that regulates tumour suppressor ... | KEEP AS NON CORE | Summary: IDA evidence from PMID:26595526 associates ELAVL1 with miRNA binding. Reason: Direct assays in the PDCD4/miR-21 system support miRNA binding, but this is a specific regulatory context subordinate to HuR's broader AU-rich target-RNA activity. |
| GO:0051260 protein homooligomerization | IDA PMID:26595526 ERK8 is a novel HuR kinase that regulates tumour suppressor ... | KEEP AS NON CORE | Summary: IDA evidence from PMID:26595526 associates ELAVL1 with protein homooligomerization. Reason: Inhibitor-based mechanistic analysis supports HuR self-association before RNA binding. Oligomerization is retained as a real enabling property but is subordinate to the core RNA-binding/stabilization activity. |
| GO:0060965 negative regulation of miRNA-mediated gene silencing | IMP PMID:26595526 ERK8 is a novel HuR kinase that regulates tumour suppressor ... | ACCEPT | Summary: IMP evidence from PMID:26595526 associates ELAVL1 with negative regulation of miRNA-mediated gene silencing. Reason: Direct binding and perturbation in the PDCD4/miR-21 system establish that HuR occupancy protects a target mRNA from miRNA-mediated silencing, a mechanistically informative adaptor/stabilization role. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:16126846 Involvement of KSRP in the post-transcriptional regulation o... | ACCEPT | Summary: IDA evidence from PMID:16126846 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:1990904 ribonucleoprotein complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS evidence from GO_REF:0000024 associates ELAVL1 with ribonucleoprotein complex. Reason: ELAVL1 demonstrably occupies multiple mRNPs, but this very broad complex term does not identify a stable obligate complex or a distinct core function. |
| GO:0005515 protein binding | IPI PMID:17632515 Identification and mechanistic characterization of low-molec... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:17632515 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:17632515 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0005654 nucleoplasm | IDA PMID:17632515 Identification and mechanistic characterization of low-molec... | ACCEPT | Summary: IDA evidence from PMID:17632515 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005829 cytosol | IDA PMID:17632515 Identification and mechanistic characterization of low-molec... | ACCEPT | Summary: IDA evidence from PMID:17632515 associates ELAVL1 with cytosol. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:23519412 The structure of the ARE-binding domains of Hu antigen R (Hu... | ACCEPT | Summary: IDA evidence from PMID:23519412 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:8626503 Cloning and characterization of HuR, a ubiquitously expresse... | ACCEPT | Summary: IDA evidence from PMID:8626503 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0042803 protein homodimerization activity | IPI PMID:17632515 Identification and mechanistic characterization of low-molec... | KEEP AS NON CORE | Summary: IPI evidence from PMID:17632515 associates ELAVL1 with protein homodimerization activity. Reason: Inhibitor-based mechanistic analysis supports HuR self-association before RNA binding. Oligomerization is retained as a real enabling property but is subordinate to the core RNA-binding/stabilization activity. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: HDA evidence from PMID:19946888 associates ELAVL1 with membrane. Reason: Recovery in a broad NK-cell membrane proteome does not establish functional membrane residence for a soluble nucleocytoplasmic RNA-binding protein; the observation is likely peripheral or fractionation-associated. |
| GO:0003730 mRNA 3'-UTR binding | ISS GO_REF:0000024 | MODIFY | Summary: ISS evidence from GO_REF:0000024 associates ELAVL1 with mRNA 3'-UTR binding. Reason: The mRNA 3'-UTR binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:2000036 regulation of stem cell population maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS evidence from GO_REF:0000024 associates ELAVL1 with regulation of stem cell population maintenance. Reason: This orthology-propagated process is biologically plausible as a transcript- and cell-context-dependent downstream consequence of ELAVL1 RNA regulation, but it does not define the protein's core molecular activity. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MODIFY | Summary: HDA evidence from PMID:22658674 associates ELAVL1 with RNA binding. Reason: The RNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MODIFY | Summary: HDA evidence from PMID:22681889 associates ELAVL1 with RNA binding. Reason: The RNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0003725 double-stranded RNA binding | IDA PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | UNDECIDED | Summary: IDA evidence from PMID:21266579 associates ELAVL1 with double-stranded RNA binding. Reason: The cached full article is accessible but does not name HuR/ELAVL1 in its searchable body; the relevant assay may be confined to supplementary proteomic evidence. Because this is an experimental curator annotation, it is left unresolved rather than removed. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450387 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450387 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450494 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450494 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450533 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450533 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450550 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450550 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-450595 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450595 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-517674 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-517674 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-517705 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-517705 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9921507 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-9921507 associates ELAVL1 with nucleoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-450595 | ACCEPT | Summary: TAS evidence from Reactome:R-HSA-450595 associates ELAVL1 with cytosol. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:23056314 Angiogenesis inhibitor vasohibin-1 enhances stress resistanc... | ACCEPT | Summary: IDA evidence from PMID:23056314 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0005634 nucleus | IDA PMID:14517288 Stabilization of urokinase and urokinase receptor mRNAs by H... | ACCEPT | Summary: IDA evidence from PMID:14517288 associates ELAVL1 with nucleus. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0005737 cytoplasm | IDA PMID:14517288 Stabilization of urokinase and urokinase receptor mRNAs by H... | ACCEPT | Summary: IDA evidence from PMID:14517288 associates ELAVL1 with cytoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0019901 protein kinase binding | IPI PMID:14517288 Stabilization of urokinase and urokinase receptor mRNAs by H... | KEEP AS NON CORE | Summary: IPI evidence from PMID:14517288 associates ELAVL1 with protein kinase binding. Reason: Regulated association with kinases is supported and controls HuR phosphorylation/shuttling, but kinase binding is regulatory and context-dependent rather than the core RNA-recognition activity. |
| GO:0035925 mRNA 3'-UTR AU-rich region binding | IDA PMID:14517288 Stabilization of urokinase and urokinase receptor mRNAs by H... | ACCEPT | Summary: IDA evidence from PMID:14517288 supports ELAVL1 binding to AU-rich regions in mRNA 3-prime UTRs. Reason: This is the defining ELAVL1 molecular activity, supported by founding recombinant-protein binding, multiple target-RNA studies, RNAcompete, and tandem-RRM structural analysis. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IDA PMID:14517288 Stabilization of urokinase and urokinase receptor mRNAs by H... | ACCEPT | Summary: IDA evidence from PMID:14517288 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:0003723 RNA binding | IDA PMID:21613615 Coordinate regulation of GATA-3 and Th2 cytokine gene expres... | MODIFY | Summary: IDA evidence from PMID:21613615 associates ELAVL1 with RNA binding. Reason: The RNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0045727 positive regulation of translation | IDA PMID:21613615 Coordinate regulation of GATA-3 and Th2 cytokine gene expres... | KEEP AS NON CORE | Summary: IDA evidence from PMID:21613615 associates ELAVL1 with positive regulation of translation. Reason: The experimental curator annotation is consistent with HuR-dependent expression of GATA3 and Th2 cytokines, but translational promotion is target- and immune-context-specific rather than a universal core outcome. |
| GO:0048255 mRNA stabilization | IDA PMID:21613615 Coordinate regulation of GATA-3 and Th2 cytokine gene expres... | ACCEPT | Summary: IDA evidence from PMID:21613615 associates ELAVL1 with mRNA stabilization. Reason: Direct binding, decay-chase, depletion, reporter, and recruitment experiments across multiple target transcripts establish mRNA stabilization as a core ELAVL1 process. |
| GO:0005515 protein binding | IPI PMID:17932509 Proteomic and functional analysis of Argonaute-containing mR... | MARK AS OVER ANNOTATED | Summary: IPI evidence from PMID:17932509 associates ELAVL1 with protein binding. Reason: The interaction reported by PMID:17932509 may be valid, but generic protein binding does not describe the partner, RNA dependence, or functional consequence and should not be presented as a defining ELAVL1 molecular function. |
| GO:0003723 RNA binding | IDA PMID:19561594 Rapid and systematic analysis of the RNA recognition specifi... | MODIFY | Summary: IDA evidence from PMID:19561594 associates ELAVL1 with RNA binding. Reason: The RNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
| GO:0005737 cytoplasm | IDA PMID:19029303 Control of c-myc mRNA stability by IGF2BP1-associated cytopl... | ACCEPT | Summary: IDA evidence from PMID:19029303 associates ELAVL1 with cytoplasm. Reason: ELAVL1 is a nucleocytoplasmic shuttling protein, and both nuclear/nucleoplasmic RNA engagement and cytoplasmic/cytosolic target regulation are integral to its function. |
| GO:0048255 mRNA stabilization | IMP PMID:19029303 Control of c-myc mRNA stability by IGF2BP1-associated cytopl... | ACCEPT | Summary: IMP evidence from PMID:19029303 associates ELAVL1 with mRNA stabilization. Reason: Direct binding, decay-chase, depletion, reporter, and recruitment experiments across multiple target transcripts establish mRNA stabilization as a core ELAVL1 process. |
| GO:0070935 3'-UTR-mediated mRNA stabilization | IMP PMID:19029303 Control of c-myc mRNA stability by IGF2BP1-associated cytopl... | ACCEPT | Summary: IMP evidence from PMID:19029303 supports stabilization mediated through target mRNA 3-prime UTRs. Reason: 3-prime-UTR-dependent stabilization is the principal direct biological outcome of HuR AU-rich-element binding and is reproduced across many human target transcripts. |
| GO:0003729 mRNA binding | TAS PMID:10660597 Purification and characterization of beta-adrenergic recepto... | MODIFY | Summary: TAS evidence from PMID:10660597 associates ELAVL1 with mRNA binding. Reason: The mRNA binding assignment is true but unnecessarily broad for ELAVL1. Direct biochemical and structural evidence supports the more informative AU-rich 3-prime-UTR binding term. Proposed replacements: mRNA 3'-UTR AU-rich region binding |
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Download this section (compressed HTML)Q: What RNA-sequence, structure, modification, and partner combinations switch HuR from stabilization to destabilization or translational control?
Q: Which protein partners are directly recruited by HuR as an adaptor rather than co-recovered through a shared RNA?
Q: Does isoform 2 differ from canonical HuR in target selection, oligomerization, localization, or stimulus-dependent shuttling?
Q: What experiment underlies the PMID:21266579 double-stranded-RNA-binding annotation?
Experiment: Use a barcoded 3-prime-UTR library spanning AU/U-rich sequence, structure, and spacing variants in ELAVL1-null cells rescued with wild-type or RRM mutants; measure binding, RNA half-life, and translation with and without KSRP, TTP, AGO2, and YBX1 perturbation.
Hypothesis: Local RNA sequence and structure together with defined protein competitors determine whether HuR occupancy stabilizes or destabilizes a transcript.
Type: Massively parallel RNA-binding and transcript-fate assay
Experiment: Map HuR interactors by crosslinking mass spectrometry and affinity purification with matched RNase conditions, then test separation-of-function interface mutants for partner recruitment, target stabilization, and miRNA antagonism.
Hypothesis: HuR protein-RNA adaptor activity depends on direct partner contacts that can be separated from RNA-mediated co-complex recovery.
Type: Interaction-interface mapping and functional complementation
Experiment: Generate isoform-specific knock-in tags and matched rescue constructs, then compare RNA targets, partner proteomes, oligomerization, and live-cell trafficking under basal, oxidative-stress, and kinase-activation conditions.
Hypothesis: ELAVL1 isoform 2 has altered RNP assembly or nucleocytoplasmic trafficking.
Type: Isoform-resolved RNP profiling and live-cell localization
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The sequence and structural rules that determine whether a HuR-bound transcript is stabilized, destabilized, or translationally regulated remain incompletely resolved.
OPEN BIOLOGY MF_DARK
What is known: AU-rich and U-rich recognition is well established, but target outcome varies with RNA context, competing RNA-binding proteins, miRNAs, and HuR post-translational state.
Significance: Resolving outcome determinants is necessary to predict functional consequences from HuR occupancy rather than treating all binding events as stabilizing.
What would resolve it: Combine purified-protein binding and structure-probing with matched time-resolved RNA half-life, ribosome-profiling, and partner-perturbation assays across engineered 3-prime-UTR sequence libraries.
Provenance (the field's own admissions):
Gap: The reported double-stranded-RNA-binding activity cannot be verified from the locally available article body.
OPEN CURATION MF_DARK
What is known: PMID:21266579 is available in full text but does not name ELAVL1/HuR in searchable article text; the assay may be present only in supplementary proteomic data.
Significance: Verification is needed to decide whether double-stranded RNA binding is a genuine additional activity or a proteomic association artifact.
What would resolve it: Recover and inspect the original supplementary tables and assay details, then repeat binding with purified ELAVL1 and defined double-stranded versus single-stranded RNA controls.
Provenance (the field's own admissions):
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