Affinage

Showing ELAVL1 — HUR is a alias.

ELAVL1

ELAV-like protein 1 · UniProt Q15717

Length
326 aa
Mass
36.1 kDa
Annotated
2026-06-09
100 papers in source corpus 48 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELAVL1/HuR is a ubiquitously expressed RNA-binding protein that post-transcriptionally controls gene expression by selectively binding AU-rich elements (AREs) in target mRNA 3'-UTRs and antagonizing ARE-mediated decay to stabilize transcripts (PMID:11289308, PMID:10811625). Structurally it uses three RNA recognition motifs, with RRM3 contributing both RNA contacts and a dimerization interface; RNA binding drives the flexible apo-protein into a compact conformation, and both RRM3 dimerization and RNA binding are required for full activity (PMID:30418581). Through these activities HuR governs proliferation by stabilizing cyclin A and cyclin B1 mRNAs in a cell cycle-dependent manner (PMID:10811625), and orchestrates a broad pro-survival program by stabilizing or enhancing translation of anti-apoptotic mRNAs (ProTα, SIRT1, Bcl-2, Mcl-1, XIAP) (PMID:17534146, PMID:21102524) while repressing pro-death targets such as Fas (PMID:25678597). Beyond mRNA stability, HuR regulates cap-independent translation via IRES (XIAP) (PMID:21102524), alternative splicing and isoform selection (Apob pre-mRNA, glutaminase GLS) (PMID:32546794, PMID:38965208), and nucleo-cytoplasmic export of lncRNAs (RMRP via CRM1, HOTAIR) (PMID:27198227, PMID:37872163), and supports telomerase assembly by binding TERC RNA and promoting C106 methylation (PMID:29880812). HuR is predominantly nuclear but translocates to the cytoplasm in response to proliferative, stress, and metabolic cues; this shuttling is governed by phosphorylation—Cdk1-type phosphorylation at S242 retains HuR in the nucleus and limits target binding (PMID:18948743), while PKCβ and p38 MAPK signaling promote its cytoplasmic activity (PMID:20599775, PMID:35594792)—and by AMPK-dependent control of cytoplasmic HuR levels (PMID:11971974). In vivo, conditional and tissue-specific knockouts establish essential roles in placental and embryonic development (PMID:19307312), spermatogenesis (PMID:21737689), adipose lipolysis and adipogenesis (PMID:31147543, PMID:31924774), hepatic lipid metabolism (PMID:32546794), and cardiac and vascular function (PMID:31373621, PMID:34747371). HuR abundance and activity are themselves tightly regulated: miR-519 represses its translation (PMID:19088191), lncRNA/ceRNA sponges such as OIP5-AS1 sequester it (PMID:26819413), and TRIM21- and ECRG2-driven ubiquitination targets it for proteasomal degradation (PMID:26434587, PMID:32678213).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established that HuR is a sequence-specific ARE-binding protein that physically stabilizes target mRNAs, defining its core molecular activity and linking it to cell cycle progression.

    Evidence Gel-shift/supershift assays, antisense knockdown, and mRNA half-life measurement on cyclin A and B1 in synchronized cells

    PMID:10811625 PMID:11289308

    Open questions at the time
    • Did not resolve how nuclear HuR reaches cytoplasmic targets
    • Mechanism of decay antagonism at the molecular level not defined
  2. 2002 High

    Showed that metabolic signaling through AMPK sets the level of cytoplasmic HuR, connecting energy status to ARE-mRNA stabilization.

    Evidence Dominant-negative/constitutively active AMPK adenovirus, cytoplasmic fractionation, RNA binding and half-life assays

    PMID:11971974

    Open questions at the time
    • Direct vs. indirect AMPK effect on HuR not distinguished
    • No phosphosite mapping in this study
  3. 2003 High

    Extended HuR target repertoire to inflammatory (COX-2) and oncogenic (beta-catenin) transcripts and provided in vivo evidence for a pro-tumorigenic role.

    Evidence RNA immunoprecipitation, RNAi/antisense knockdown, expression profiling, and xenograft tumor models

    PMID:12704185 PMID:14562043

    Open questions at the time
    • beta-catenin stabilization mechanism not deeply dissected
    • Upstream signals controlling target selectivity unclear
  4. 2007 Medium

    Consolidated HuR as a master regulator of an anti-apoptotic program acting through both mRNA stabilization and translational enhancement.

    Evidence Review integrating RNA-IP, translation, and stability assays for ProTα, SIRT1, Bcl-2, Mcl-1

    PMID:17534146

    Open questions at the time
    • Relative contribution of stability vs. translation per target not quantified
    • Compiled from multiple studies rather than one reconstituted system
  5. 2008 High

    Identified phosphorylation as the switch controlling HuR localization and activity, showing S242 phosphorylation enforces nuclear retention and dampens target binding/proliferation.

    Evidence S242A/S242D mutagenesis with fractionation, RIP, mRNA half-life, and proliferation assays; plus miR-519 reporter, polysome, and rescue assays

    PMID:18948743 PMID:19088191

    Open questions at the time
    • Physiological kinase for S242 not definitively assigned in these studies
    • How phosphorylation alters RNA affinity structurally unknown
  6. 2009 High

    Genetic ablation demonstrated that HuR is essential for development, with target mRNAs guiding placental, skeletal, and splenic morphogenesis, and expanded targets to the epigenetic enzyme DNMT3b.

    Evidence Conditional knockout mice with expression and HuR-RNA association assays; RNP-IP, biotin pulldown, and methylation analysis for DNMT3b

    PMID:19270063 PMID:19307312

    Open questions at the time
    • Which target mRNAs are rate-limiting for each developmental phenotype not resolved
    • Stress-induced complex dissociation mechanism (cisplatin) not defined
  7. 2010 High

    Broadened HuR's mechanistic scope to IRES-mediated translation (XIAP) and revealed that posttranslational methylation reverses its effect on a target (MAT2A), introducing PKCβ as an activating kinase.

    Evidence UV cross-linking, polysome profiling, IRES reporter, apoptosis rescue; RIP and SAM manipulation; RNP-IP with PKCβ inhibition in diabetic rat retina

    PMID:20102719 PMID:20599775 PMID:21102524

    Open questions at the time
    • Methyltransferase responsible for HuR methylation not identified here
    • Structural basis for methylation-dependent functional reversal unknown
  8. 2011 High

    Tissue-specific knockout showed HuR controls translation of germ cell mRNAs (Hspa2) required for meiosis, and clarified translational regulation vs. P-body sequestration for nucleolin.

    Evidence Germ cell-specific KO mice with RNA binding/translation assays; RIP, MS2 RNA tracking to P-bodies, Ago-IP and miR-494 competition

    PMID:21737689 PMID:21859890

    Open questions at the time
    • How HuR selects translational vs. stability mode per target not defined
    • Trigger for nucleolin mRNA mobilization to P-bodies upon HuR loss unclear
  9. 2016 High

    Revealed non-canonical roles in lncRNA nuclear export (RMRP via CRM1) and showed that lncRNA sponges (OIP5-AS1) and nuclear import machinery couple HuR to broader RNA and protein trafficking.

    Evidence Affinity RNA pulldown-MS, RIP, CRM1 inhibition, mitochondrial fractionation; MS2 pulldown and competition assays; nuclear import and reporter assays

    PMID:26819413 PMID:27198227 PMID:27609837

    Open questions at the time
    • How HuR is partitioned between export and stabilization functions unknown
    • OIP5-AS1 sponge effect characterized in a single lab
  10. 2019 High

    Crystal/NMR/SAXS structural work defined RRM3 as both an RNA-contacting and dimerization module and established that RNA binding induces a compact conformation required for function.

    Evidence RRM3 crystal structures (free and RNA-bound), NMR, SAXS, mutagenesis, and target mRNA assays in cells

    PMID:30418581

    Open questions at the time
    • Full-length multi-RRM/RNA complex structure not solved
    • How dimerization tunes target selectivity in vivo not established
  11. 2020 High

    In vivo conditional knockouts across adipose, liver, and heart defined HuR as a metabolic and cardiovascular regulator acting through distinct RNA elements (splicing, 5'/3'-UTR translation, stability) on multiple targets.

    Evidence Tissue-specific KO mice (adipose, hepatocyte, cardiomyocyte, endothelial) with RIP, mRNA stability, translation, splicing, and physiological readouts

    PMID:31147543 PMID:31373621 PMID:31924774 PMID:32546794 PMID:34747371

    Open questions at the time
    • How a single protein achieves opposite effects (stabilize PLB vs destabilize β1-AR) on different targets unresolved
    • Tissue-specific cofactors directing target choice not identified
  12. 2022 High

    Defined HuR roles in metabolic reprogramming (GLS splicing), miRNA biogenesis (miR-122), developmental specification (Draxin), and demonstrated druggability via small molecules, structural inhibitors, and bioPROTAC degraders.

    Evidence ELAVL1 knockdown with isoform/flux analysis; PLK1 axis and HCV models; chick embryo RIP/rescue; NMR-guided DHTS inhibitor and VHH-TRIM21 bioPROTAC with in vivo proteome readout

    PMID:28934484 PMID:36189921 PMID:36512502 PMID:37925433 PMID:38965208

    Open questions at the time
    • Generalizability of PLK1-HuR-miRNA axis beyond HCV unknown
    • Selectivity of degrader and inhibitor across the full HuR target proteome not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HuR integrates phosphorylation, methylation, ubiquitination, miRNA, and lncRNA inputs to select among stabilization, translational, splicing, and export outcomes on a per-target basis remains unresolved.
  • No unified code linking PTM state to functional outcome
  • Determinants of opposite regulatory effects on distinct targets undefined
  • Full-length protein-RNA complex structure and in-cell conformational states unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005829 cytosol 5 GO:0005634 nucleus 4
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-9612973 Autophagy 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3
Partners
AMPKCRM1ECRG2LINC00941OIP5-AS1TRIM21TRN2

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 HuR selectively binds AU-rich elements (AREs) in the 3' untranslated regions of target mRNAs and stabilizes them, antagonizing ARE-mediated mRNA degradation. Newly identified protein ligands to HuR modulate its function in normal and stressed cells. RNA-binding assays, overexpression in cultured cells, review of experimental literature Cellular and molecular life sciences : CMLS High 11289308
2000 HuR directly binds the 3'-UTRs of cyclin A and cyclin B1 mRNAs in a cell cycle-dependent manner, stabilizing these transcripts during S and G2 phases and thereby promoting cell proliferation. HuR translocates from the nucleus to the cytoplasm during late G1, S, and G2 phases. Gel-shift assays with radiolabeled RNA, anti-HuR supershift assays, antisense HuR knockdown, mRNA half-life measurement, cell cycle synchronization The EMBO journal High 10811625
2002 AMP-activated kinase (AMPK) regulates the level of cytoplasmic HuR: AMPK inhibition increases cytoplasmic HuR and enhances HuR binding to p21, cyclin B1, and cyclin A mRNAs, elevating their expression; AMPK activation reduces cytoplasmic HuR and decreases target mRNA stability. Dominant-negative and constitutively active AMPK adenovirus infection, cytoplasmic fractionation, RNA-protein binding assays, mRNA half-life measurement Molecular and cellular biology High 11971974
2003 HuR binds to three specific sites in the 3'-UTR of COX-2 mRNA and stabilizes it post-transcriptionally. HuR knockdown by RNAi or antisense attenuated serum withdrawal-induced COX-2 mRNA and protein accumulation. RNA immunoprecipitation from cell extracts, RNAi and antisense knockdown, mRNA level quantification The Journal of biological chemistry High 12704185
2003 HuR regulates beta-catenin mRNA in colon carcinoma cells; HuR overexpression increases tumor growth in vivo, while HuR knockdown (siRNA or antisense) slows growth, establishing HuR as a positive regulator of colon carcinogenesis through target mRNA stabilization. Immunohistochemistry, gene expression profiling, RNAi/antisense knockdown, xenograft tumor model Oncogene Medium 14562043
2007 HuR promotes cell survival by binding and stabilizing/enhancing translation of mRNAs encoding anti-apoptotic proteins including ProTα, SIRT1, Bcl-2, and Mcl-1, orchestrating a broad anti-apoptotic gene expression program. RNA immunoprecipitation, translation assays, mRNA stability assays reviewed from multiple studies Cell cycle (Georgetown, Tex.) Medium 17534146
2008 Phosphorylation of HuR at serine 242 inhibits its cytoplasmic localization and mRNA-stabilizing function. The non-phosphorylatable S242A mutant accumulates in the cytoplasm, shows increased association with cyclin A2 and B1 mRNAs, stabilizes these mRNAs, and heightens cell proliferation. The phosphomimetic S242D mutant remains nuclear under all conditions. Site-directed mutagenesis of HuR hinge region, subcellular fractionation, RNA immunoprecipitation, mRNA half-life assay, cell proliferation assay Cell cycle (Georgetown, Tex.) High 18948743
2008 miR-519 represses HuR translation by interacting with its coding region and 3'-UTR, reducing HuR protein abundance without altering HuR mRNA levels, and consequently decreasing HuR-regulated target mRNA levels and cell proliferation. miR-519 precursor/antisense overexpression, reporter constructs with HuR coding region or 3'-UTR, polysome profiling, [3H]-thymidine incorporation, RNAi rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 19088191
2009 HuR binds to the 3'-UTR of DNMT3b mRNA, stabilizing it and increasing DNMT3b expression. Cisplatin treatment dissociates the HuR-DNMT3b mRNA complex, promoting DNMT3b mRNA decay, reducing DNMT3b protein, and lowering global DNA methylation. Ribonucleoprotein immunoprecipitation followed by RT-qPCR, biotinylated RNA pulldown with western blot, mRNA decay assay, methylation analysis Nucleic acids research High 19270063
2009 Genetic ablation of HuR causes embryonic lethality at midgestation due to placental labyrinth defects; conditional deletion in embryonic cells reveals HuR controls posttranscriptional regulation of transcription and growth factor mRNAs guiding placental morphogenesis, skeletal specification, and splenic ontogeny. Conditional knockout mice (embryonic and endothelial compartments), gene expression analysis, HuR-RNA association assays Molecular and cellular biology High 19307312
2010 HuR promotes XIAP translation via the IRES element in XIAP mRNA 5'-UTR: HuR binds XIAP IRES in vitro and in vivo and stimulates recruitment of XIAP mRNA into polysomes, contributing to HuR-mediated cytoprotection from apoptosis. UV cross-linking, RNA immunoprecipitation, polysome profiling, IRES-reporter assay, etoposide-apoptosis rescue experiment Oncogene High 21102524
2010 Methylated HuR (methyl-HuR) acts as an inhibitor of MAT2A mRNA stability, whereas non-methylated HuR promotes MAT2A mRNA stability. S-adenosylmethionine shifts the balance between methyl-HuR and HuR, regulating hepatic differentiation-dependent MAT expression. RNA immunoprecipitation, mRNA stability assays, immunofluorescence, manipulation of SAM levels in hepatic cell models Gastroenterology Medium 20102719
2010 PKCβ phosphorylates/activates HuR in the retina under diabetic conditions, leading to HuR binding to VEGF mRNA and elevated VEGF protein expression; PKCβ inhibition blocks this pathway. Immunoprecipitation coupled to RT-PCR for RNP complexes, PKCβ inhibitor treatment in diabetic rat model, western blot for HuR phosphorylation Biochemical pharmacology Medium 20599775
2011 Targeted deletion of HuR in germ cells causes male sterility due to spermatocyte death at meiosis and spermatid elongation failure. HuR specifically binds Hspa2 mRNA and controls its expression at the translational level in germ cells. Conditional germ cell-specific knockout mice, target gene approach, RNA binding assay, translational regulation analysis Molecular biology of the cell High 21737689
2011 HuR interacts with nucleolin mRNA 3'-UTR and promotes nucleolin translation without affecting mRNA levels; loss of HuR mobilizes nucleolin mRNA to processing bodies (PBs). HuR and miR-494 competitively regulate nucleolin expression, and HuR-driven cell proliferation is partly mediated through increased nucleolin expression. RIP, MS2-tagged RNA tracking to PBs, miRNA immunoprecipitation with Argonaute, reporter assay, HuR/miR-494 competitive overexpression/knockdown Molecular and cellular biology High 21859890
2016 HuR binds lncRNA RMRP in the nucleus and mediates its CRM1-dependent export to the cytoplasm. After RMRP import into mitochondria, GRSF1 binds RMRP and maintains its mitochondrial abundance, supporting oxygen consumption and mitochondrial DNA replication priming. Affinity RNA pulldown with mass spectrometry, RNA immunoprecipitation, CRM1 inhibition, mitochondrial fractionation, oxygen consumption rate measurement Genes & development High 27198227
2016 lncRNA OIP5-AS1 (cyrano) acts as a sponge/ceRNA for HuR: high OIP5-AS1 sequesters HuR away from its target mRNAs, preventing HuR-mediated proliferative mRNA stabilization, while HuR stabilizes OIP5-AS1. miR-424 competes with HuR for binding to OIP5-AS1. MS2-hairpin RNA tagging and pulldown, miRNA/HuR competition assay, RNA immunoprecipitation, cell proliferation assays with OIP5-AS1 modulation Nucleic acids research Medium 26819413
2016 HuR controls the expression of multiple nuclear import machinery components, and is required for nuclear import of CRABP2 (via classical-like NLS) and heregulin-induced nuclear translocation of NFκB p65, thereby regulating transcriptional activities of RAR and NFκB. HuR knockdown, subcellular localization assays, nuclear import assays, transcriptional reporter assays Journal of cell science Medium 27609837
2017 The natural product dihydrotanshinone-I (DHTS) binds to residues within HuR RRM1 and RRM2 domains (identified by NMR titration and molecular dynamics), stabilizing HuR in a locked conformation that competitively inhibits RNA binding. In cells, DHTS preferentially displaces HuR from mRNAs with short 3'-UTRs or lower ARE density. NMR titration, molecular dynamics simulation, RNA electrophoretic mobility shift assay, AlphaScreen binding assay, RIP-chip transcriptome-wide analysis, xenograft model Nucleic acids research High 28934484
2018 HuR promotes ferroptosis in hepatic stellate cells by binding AU-rich elements in the 3'-UTR of BECN1 (Beclin1) mRNA, stabilizing it and activating autophagy/ferritinophagy. ELAVL1 expression is induced by inhibition of ubiquitin-proteasome pathway during ferroptosis induction. siRNA/plasmid manipulation of ELAVL1, BECN1 3'-UTR deletion analysis, RIP assay, autophagy flux assays, mouse model of liver fibrosis with HSC-specific ELAVL1 knockdown Autophagy High 30081711
2019 HuR comprises three RNA recognition motifs (RRMs); RRM3 mediates canonical RNA binding AND a dimerization interface on its α-helical face. Full-length HuR adopts a compact conformation upon RNA binding (free protein is flexible by NMR/SAXS). RRM3 dimerization and RNA binding are both required for HuR functional activity in vitro and in cells. Crystal structures of RRM3 free and RNA-bound, NMR, SAXS, biochemical binding assays, RRM3 mutagenesis, target mRNA level assays in human cells Nucleic acids research High 30418581
2018 HuR binds the 3'-UTR of TIN2 mRNA, destabilizing TIN2 mRNA and reducing its translation. Loss of HuR during replicative senescence increases TIN2 expression, enhancing mitochondrial TIN2 localization and ROS production, thereby promoting cellular senescence. RIP, mRNA stability assay, HuR knockdown/overexpression, mitochondrial fractionation, ROS measurement Nucleic acids research High 29584879
2018 HuR binds TERC RNA and promotes TERC C106 methylation, facilitating TERC/TERT complex assembly and telomerase activity. Dyskeratosis congenita-related TERC mutations (U100A, G107U, GC107/108AG) impair HuR binding, reducing C106 methylation, decreasing telomerase activity, and causing telomere shortening and hematopoietic stem cell renewal defects. RNA immunoprecipitation, methylation assays, TERC mutation analysis, HuR knockout mice (hematopoietic stem cells), telomerase activity assays Nature communications High 29880812
2018 HuR binds MEF2C mRNA and protects it from degradation, increasing MEF2C levels which in turn transcriptionally enhance SCN5A expression. HuR overexpression increased SCN5A mRNA, an effect attenuated by MEF2C siRNA. RNP immunoprecipitation (RIP), mRNA stability assay, ChIP-qPCR, EMSA, MEF2C siRNA rescue experiment Journal of the American Heart Association Medium 29678826
2019 Adipose-specific HuR knockout mice show obesity and metabolic dysfunction. HuR positively regulates ATGL (adipose triglyceride lipase) expression by promoting both mRNA stability and translation of ATGL, thereby controlling lipolysis. Adipose-specific HuR KO mice, mRNA stability assay, translation assay, RIP Nature communications High 31147543
2020 HuR forms complexes with NAFLD-relevant transcripts: it associates with intron 24 of Apob pre-mRNA to regulate alternative splicing, with the 3'-UTR of Uqcrb to regulate translation, and with the 5'-UTR of Ndufb6 mRNA to regulate NDUFB6 translation. Hepatocyte-specific HuR KO reduces APOB, UQCRB, and NDUFB6 expression, impairing lipid transport and ATP synthesis. RNA immunoprecipitation, hepatocyte-specific KO mice, adenovirus re-expression rescue, mRNA splicing analysis, translation assays Nature communications High 32546794
2020 HuR stabilizes PLB (phospholamban) mRNA and destabilizes β1-AR mRNA in cardiomyocytes. Cardiomyocyte-specific HuR deletion mitigates isoproterenol-induced PLB expression, aggravating myocardial hypertrophy. Cardiomyocyte-specific HuR KO mouse, RIP assay for PLB and β1-AR mRNAs, mRNA stability assays Cardiovascular research High 31373621
2020 Fat-specific knockout of HuR enhances adipogenic gene programs and causes depot-specific phenotypes, including repression of myogenesis in brown fat, enhanced inflammation in epididymal white fat, and induction of browning in inguinal white fat. HuR inhibits adipogenesis at least partly by modulating stability of Insig1 mRNA. Fat-specific HuR KO mice, RNA-seq, mRNA stability assays, in vitro adipogenesis assays with HuR knockdown/overexpression Nature communications High 31924774
2020 HuR suppresses Fas (death receptor) mRNA translation by binding to two AU-rich domains in the Fas mRNA 3'-UTR, preventing Fas-mediated apoptosis in hepatocellular carcinoma cells. Hydrodynamic transfection of HuR plasmid in mice induced Fas downregulation and resistance to Fas agonist. RIP, 3'-UTR reporter assay, HuR silencing and Fas protein/surface expression assays, in vivo hydrodynamic transfection Molecular cancer research : MCR High 25678597
2015 HuR/ELAVL1 is the predominant RNA-binding protein associating with the IFN-β mRNA ARE; reduced HuR expression or chemical inhibition severely impairs the type I IFN response in multiple cell types, demonstrating HuR as a key potentiator of innate antiviral signaling through IFN-β mRNA stabilization. Affinity proteomic pulldown of IFN-β ARE with mass spectrometry, HuR knockdown, chemical inhibition, type I IFN response measurement in fibroblast-like synoviocytes European journal of immunology High 25678110
2015 ECRG2 tumor suppressor negatively regulates HuR by promoting its ubiquitination and proteasomal degradation; ECRG2 expression reduces XIAP mRNA stability through HuR, inducing apoptosis. Cancer-derived ECRG2 V30E mutant fails to degrade HuR or suppress XIAP. Ubiquitination assay, HuR stability measurement, XIAP mRNA stability assay, caspase activation, mutant analysis Oncogene Medium 26434587
2016 In myogenesis, HuR must translocate to the cytoplasm to stabilize myogenic factor mRNAs; cytoplasmic HuR accumulation requires its dissociation from the nuclear import factor Transportin 2 (TRN2), triggered by proteolytic cleavage of a portion of cytoplasmic HuR. Review of experimental findings from the same group: cleavage assays, Transportin-2 interaction assays, myogenesis models Biochimica et biophysica acta Medium 21315776
2014 HuR binds the 3'-UTR of ABCA1 mRNA and promotes ABCA1 translation, increasing cholesterol efflux. Cholesterol levels regulate HuR expression, localization, and its interaction with ABCA1 mRNA. RNA immunoprecipitation, HuR knockdown, cholesterol efflux assay, cell fractionation Journal of lipid research Medium 24729624
2014 HSF1 regulates β-catenin expression at the translational level by controlling HuR levels; HuR in turn controls β-catenin translation. mTOR phosphorylation of HSF1 at S326 promotes β-catenin expression through a mechanism requiring HuR. HSF1 gain/loss-of-function, HuR level quantification, translation assays, mTOR knockdown with HuR-dependent rescue Oncogene Medium 24954509
2018 HuR binds the 3'-UTR of BECN1 mRNA via the F3 AU-rich region, stabilizing it and activating autophagy. Internal deletion of the F3 region abrogated HuR-mediated BECN1 mRNA stability and ferroptosis. RIP assay, BECN1 3'-UTR deletion constructs, mRNA stability assay, autophagy flux monitoring Autophagy High 30081711
2022 HuR regulates glutaminase (GLS) mRNA alternative splicing and isoform translation/stability in breast cancer. ELAVL1 knockdown reduces KGA isoform and increases GAC levels, enhancing glutamine anaplerosis into the TCA cycle. Combining GLS chemical inhibition with ELAVL1 silencing synergistically decreases breast cancer cell growth. ELAVL1 knockdown, isoform quantification by RT-PCR, metabolic flux analysis (glutamine anaplerosis), cell viability assays Nature communications High 38965208
2022 HuR is required for maintenance of cranial neural crest specification by stabilizing Draxin mRNA; Elavl1 perturbation reduces Draxin mRNA levels and causes premature neural crest delamination, and exogenous Draxin rescues the specification defects. siRNA/antisense perturbation in chick embryos, RNA-seq, RIP, RNA decay measurement, proximity ligation assay, rescue with exogenous Draxin eLife High 36189921
2018 HuR binds HuR (ELAVL1) mRNA 3'-UTR and upregulates TRIM21 translation, while TRIM21 degrades HuR protein in response to UV radiation, constituting a negative feedback loop that regulates p53 levels in genotoxic stress. RIP showing HuR binding to TRIM21 mRNA 3'-UTR, TRIM21 ubiquitination of HuR assay, cell proliferation/colony formation, DHTS inhibitor treatment Scientific reports Medium 32678213
2022 PLK1 phosphorylates and modulates ELAVL1/HuR availability; HuR in turn binds to the 3'-end of miR-122, promoting its biogenesis and consequently HCV proliferation. PLK1 inhibition by rigosertib reduces HuR-miR-122 signaling and HCV replication. Kinase inhibitor library screening, rescue experiments with HuR overexpression/knockdown, HCV mutant with low miR-122 dependency, replicon and infectious cell models, in vivo replicon-harboring mice Proceedings of the National Academy of Sciences of the United States of America High 36512502
2021 HuR binds to AMPKα1 and AMPKα2 mRNAs in smooth muscle cells, increasing their stability and translation; smooth muscle-specific HuR KO reduces p-AMPK and LC3II while increasing p62, causing defective autophagy and enhanced atherosclerosis. Smooth muscle-specific HuR KO mice, RNA immunoprecipitation, mRNA stability assay, autophagy markers, atherosclerosis model Cell death & disease High 33837179
2022 LINC00941 forms an RNA-protein complex with ELAVL1/HuR to inhibit autophagosome-lysosome fusion. The LINC00941-ELAVL1 complex controls stability of EZH2, STAT1, and FOXK1 mRNAs, thereby blocking autophagy and promoting pulmonary fibrosis. RNA affinity isolation, RIP, RNase-RIP, half-life analysis, ubiquitination experiments, autophagic flux monitoring, RIP-seq, rescue experiments Autophagy Medium 35427207
2019 WTAP-mediated m6A modification of ETS1 mRNA leads to its post-transcriptional suppression; HuR is implicated as an RNA stabilizer in this pathway. m6A modification reduces ETS1 mRNA stability in an HuR-dependent manner in HCC. MeRIP assay, RIP assay, dual luciferase reporter, m6A dot blot, ChIP Molecular cancer Low 31438961
2020 HuR binds Cx40 mRNA in cardiac endothelial cells and stabilizes it; HuR deficiency in diabetic mice reduces Cx40 expression, contributing to coronary microvascular dysfunction. Endothelial-specific HuR-KO mice display decreased coronary flow velocity reserve and capillary density. Endothelial-specific HuR KO mice, RIP showing HuR-Cx40 mRNA binding, coronary flow velocity reserve measurement, capillary density quantification, Cx40-KO mice comparison JCI insight High 34747371
2015 HuR stabilization function during T cell activation is temporally regulated: HuR-dependent robust mRNA stabilization occurs at 4 h post-activation, coordinating stabilization of functionally related mRNA subpopulations (replicative histones, ribosomal biogenesis, cell motility), demonstrated by integrating PAR-CLIP binding data with metabolic labeling-based mRNA stability measurements. Metabolic mRNA labeling for transcription and decay rates, PAR-CLIP data integration, Jurkat T cell activation time course Nucleic acids research Medium 26490963
2022 HuR-mediated cytoplasmic translocation of HOTAIR lncRNA promotes osteoblast function: HuR is responsible for HOTAIR nucleocytoplasmic translocation during BMSC osteogenic differentiation; cytoplasmic HOTAIR acts as ceRNA for miR-214 to increase Atf4 expression. BMSC/osteoblast localization studies, HuR RIP, HuR knockdown/overexpression, transgenic mice (Prx1- and Bglap-HOTAIR), ceRNA assay Bone research Medium 37872163
2018 HuR promotes SOD2 mRNA translation specifically upon anchorage-independence; HuR translocates to the cytosol in response to matrix detachment (promoted by p38 MAPK activation), binds SOD2 mRNA, and increases its association with heavy polysomes for nascent protein synthesis. HuR siRNA knockdown, polyribosome profiling, RIP assay, p38 MAPK inhibition, nascent protein synthesis measurement Redox biology High 35594792
2018 HuR stabilizes HuR (ELAVL1) mRNA/binds HuR target mRNAs in neurons; neuron-specific HuR deficiency leads to motor neuron disease phenotype with apoptosis of pyramidal neurons and α motor neurons, TDP43 redistribution to cytosolic granules, and altered expression of HuR-regulated genes including SOD1 and Bcl2 in the brain. Inducible neuron-specific HuR KO mice, immunostaining for cleaved caspase-3, genome-wide microarray, rotarod and grip-strength tests, TDP43 localization assay Journal of immunology Medium 29760195
2015 Let-7 mimic (ssDNA complementary to let-7 binding site) enhances the affinity of HuR for a 122-nt MYC RNA containing both HuR and let-7 binding sites, demonstrating cooperative biophysical binding between HuR and a miRNA at distal mRNA binding sites. In vitro RNA binding affinity assays with let-7 mimic and recombinant HuR on MYC RNA Cell cycle (Georgetown, Tex.) Medium 26177105
2023 A single-domain antibody (VHH) binding HuR with low nanomolar affinity inhibits HuR-RNA binding; engineering this VHH into a TRIM21-based bioPROTAC degrades endogenous HuR, reversing tumor-promoting properties of cancer cells in vivo by altering the HuR-regulated proteome. VHH antibody selection and characterization, HuR-RNA binding inhibition assay, bioPROTAC engineering, in vivo xenograft degradation and proteome analysis Nature communications High 37925433
2020 HuR binds to and stabilizes EZH2, STAT1, and FOXK1 mRNAs when complexed with LINC00941, preventing autophagosome-lysosome fusion; this is demonstrated by ELAVL1 RIP-seq, RIP-PCR, and mRNA stability measurements. ELAVL1 RIP-seq, RIP-PCR, mRNA stability assay, rescue experiments Autophagy Medium 35427207

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 HuR and mRNA stability. Cellular and molecular life sciences : CMLS 957 11289308
2019 WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1. Molecular cancer 529 31438961
2000 HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation. The EMBO journal 404 10811625
2018 Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells. Autophagy 394 30081711
2010 Posttranscriptional regulation of cancer traits by HuR. Wiley interdisciplinary reviews. RNA 352 21935886
2012 HuR function in disease. Frontiers in bioscience (Landmark edition) 307 22201738
2003 Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 256 14562043
2016 Posttranslational control of HuR function. Wiley interdisciplinary reviews. RNA 212 27307117
2007 Posttranscriptional orchestration of an anti-apoptotic program by HuR. Cell cycle (Georgetown, Tex.) 212 17534146
2016 HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes & development 196 27198227
2008 miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proceedings of the National Academy of Sciences of the United States of America 195 19088191
2002 AMP-activated kinase regulates cytoplasmic HuR. Molecular and cellular biology 187 11971974
2019 Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation. Molecular cancer 183 31718709
2020 Understanding and targeting the disease-related RNA binding protein human antigen R (HuR). Wiley interdisciplinary reviews. RNA 181 31970930
2009 The RNA-binding protein Elavl1/HuR is essential for placental branching morphogenesis and embryonic development. Molecular and cellular biology 174 19307312
2012 Functional interplay between RNA-binding protein HuR and microRNAs. Current protein & peptide science 165 22708488
2016 LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR. Nucleic acids research 150 26819413
2003 The RNA-binding protein HuR regulates the expression of cyclooxygenase-2. The Journal of biological chemistry 140 12704185
2011 The RNA-binding protein HuR promotes glioma growth and treatment resistance. Molecular cancer research : MCR 128 21498545
2010 HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology 115 20102719
2022 The RNA-binding protein HuR in human cancer: A friend or foe? Advanced drug delivery reviews 108 35248670
2010 The PKCbeta/HuR/VEGF pathway in diabetic retinopathy. Biochemical pharmacology 103 20599775
2011 Competitive regulation of nucleolin expression by HuR and miR-494. Molecular and cellular biology 94 21859890
2022 ATF3 -activated accelerating effect of LINC00941/lncIAPF on fibroblast-to-myofibroblast differentiation by blocking autophagy depending on ELAVL1/HuR in pulmonary fibrosis. Autophagy 89 35427207
2014 HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 87 24954509
2022 HuR as a molecular target for cancer therapeutics and immune-related disorders. Advanced drug delivery reviews 86 35817212
2020 The RNA-binding protein HuR is a negative regulator in adipogenesis. Nature communications 83 31924774
2019 HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs. Nucleic acids research 82 30418581
2017 Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic acids research 79 28934484
2010 RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation. Oncogene 77 21102524
2019 Adipose HuR protects against diet-induced obesity and insulin resistance. Nature communications 74 31147543
2014 Clinical significance of HuR expression in human malignancy. Medical oncology (Northwood, London, England) 67 25112469
2020 Hepatic HuR modulates lipid homeostasis in response to high-fat diet. Nature communications 64 32546794
2008 Modification at HuR(S242) alters HuR localization and proliferative influence. Cell cycle (Georgetown, Tex.) 63 18948743
1998 Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins. Oncogene 61 9692549
2015 Targeting the multifaceted HuR protein, benefits and caveats. Current drug targets 59 25706256
2011 The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages. Molecular biology of the cell 59 21737689
2023 Targeting the RNA-Binding Protein HuR in Cancer. Cancer research 55 37683260
2012 Regulation of the mRNA-binding protein HuR by posttranslational modification: spotlight on phosphorylation. Current protein & peptide science 52 22708484
2020 HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling. Cardiovascular research 50 31373621
2015 The RNA-binding protein HuR/ELAVL1 regulates IFN-β mRNA abundance and the type I IFN response. European journal of immunology 50 25678110
2020 HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. The Journal of clinical investigation 49 32315290
2019 The RNA Binding Protein HuR: A Promising Drug Target for Anticancer Therapy. Current cancer drug targets 48 30381077
2017 HuR promotes breast cancer cell proliferation and survival via binding to CDK3 mRNA. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 28501005
2009 The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA. Nucleic acids research 47 19270063
2016 Dysregulation of TTP and HuR plays an important role in cancers. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 27644249
2022 Circular RNA circStag1 promotes bone regeneration by interacting with HuR. Bone research 44 35361779
2015 HuR Suppresses Fas Expression and Correlates with Patient Outcome in Liver Cancer. Molecular cancer research : MCR 43 25678597
2006 HuR, an RNA-binding protein, involved in the control of cellular differentiation. In vivo (Athens, Greece) 43 16433023
2018 Loss of RNA-binding protein HuR facilitates cellular senescence through posttranscriptional regulation of TIN2 mRNA. Nucleic acids research 42 29584879
2018 HuR regulates telomerase activity through TERC methylation. Nature communications 42 29880812
2011 HuR and myogenesis: being in the right place at the right time. Biochimica et biophysica acta 41 21315776
2014 RNA binding protein HuR regulates the expression of ABCA1. Journal of lipid research 39 24729624
2014 MicroRNA-570-3p regulates HuR and cytokine expression in airway epithelial cells. American journal of clinical and experimental immunology 38 25143867
2021 The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3'-UTR of HOXC10 mRNA. The Journal of biological chemistry 37 34302808
2009 HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol. Toxicology and applied pharmacology 37 19591856
2014 Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis. Current opinion in hematology 36 24714527
2023 A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation. Nature communications 35 37925433
2022 N6-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex. Cell death and differentiation 35 35871232
2021 Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis. Cell death & disease 35 33837179
2019 HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A. Cancers 35 31847141
2018 HuR (Elavl1) and HuB (Elavl2) Stabilize Matrix Metalloproteinase-9 mRNA During Seizure-Induced Mmp-9 Expression in Neurons. Frontiers in neuroscience 33 29686606
2017 Emerging role of HuR in inflammatory response in kidney diseases. Acta biochimica et biophysica Sinica 33 28910975
2018 Complex HuR function in pancreatic cancer cells. Wiley interdisciplinary reviews. RNA 32 29452455
2013 Adaptive and maladaptive expression of the mRNA regulatory protein HuR. World journal of biological chemistry 32 24340134
2019 HuR interacts with lincBRN1a and lincBRN1b during neuronal stem cells differentiation. RNA biology 30 31345103
2015 Negative regulation of RNA-binding protein HuR by tumor-suppressor ECRG2. Oncogene 29 26434587
2023 m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR. Molecular cancer research : MCR 27 37647111
2024 HuR controls glutaminase RNA metabolism. Nature communications 26 38965208
2021 S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD. Cell death & disease 26 33753727
2021 Drug delivery approaches for HuR-targeted therapy for lung cancer. Advanced drug delivery reviews 26 34822926
2014 HuR: a promising therapeutic target for angiogenesis. Gland surgery 26 25207213
2011 UneCLIPsing HuR nuclear function. Molecular cell 25 21816340
2023 MUC16 promotes triple-negative breast cancer lung metastasis by modulating RNA-binding protein ELAVL1/HUR. Breast cancer research : BCR 24 36918912
2022 HuR as Therapeutic Target in Cancer: What the Future Holds. Current medicinal chemistry 24 34182901
2022 Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors. Cancers 24 35681645
2016 RNA-binding protein HuR regulates nuclear import of protein. Journal of cell science 24 27609837
2023 LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis. Cell death & disease 23 36849492
2021 HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes. JCI insight 22 34747371
2018 RNA Binding Protein, HuR, Regulates SCN5A Expression Through Stabilizing MEF2C transcription factor mRNA. Journal of the American Heart Association 22 29678826
2015 Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation. Nucleic acids research 22 26490963
2022 HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence. Redox biology 21 35594792
2022 CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA. Cell death discovery 20 35568705
2021 Adipocyte-specific deletion of HuR induces spontaneous cardiac hypertrophy and fibrosis. American journal of physiology. Heart and circulatory physiology 19 34018851
2020 Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis. Clinical science (London, England : 1979) 19 32478392
2023 HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation. Bone research 18 37872163
2022 PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation. Proceedings of the National Academy of Sciences of the United States of America 18 36512502
2020 HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability. Cell biochemistry and biophysics 18 32901414
2020 UBE2C mRNA expression controlled by miR-300 and HuR determines its oncogenic role in gastric cancer. Biochemical and biophysical research communications 18 33223052
2018 Endothelial HuR deletion reduces the expression of proatherogenic molecules and attenuates atherosclerosis. International immunopharmacology 18 30340104
2015 Cooperative interplay of let-7 mimic and HuR with MYC RNA. Cell cycle (Georgetown, Tex.) 18 26177105
2022 LINC00152 induced by TGF-β promotes metastasis via HuR in lung adenocarcinoma. Cell death & disease 17 36071042
2020 RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA. The Journal of biological chemistry 17 33288677
2018 Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease. Journal of immunology (Baltimore, Md. : 1950) 17 29760195
2018 Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR. Nucleic acids research 17 29939290
2020 Negative feedback regulation by HuR controls TRIM21 expression and function in response to UV radiation. Scientific reports 16 32678213
2020 The RNA-Binding Protein HuR in Digestive System Tumors. BioMed research international 16 32775456
2015 AMPK/HuR-Driven IL-20 Post-Transcriptional Regulation in Psoriatic Skin. The Journal of investigative dermatology 16 26176762
2012 HuR and translation--the missing linc(RNA). Molecular cell 16 22920290
2022 RNA-binding protein Elavl1/HuR is required for maintenance of cranial neural crest specification. eLife 15 36189921

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