Affinage

ELAVL1

ELAV-like protein 1 · UniProt Q15717

Length
326 aa
Mass
36.1 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELAVL1 (HuR) is a ubiquitously expressed RNA-binding protein that post-transcriptionally controls the stability and translation of hundreds of mRNAs governing cell proliferation, apoptosis, autophagy, and metabolism. Its three RRM domains bind AU-rich and U-rich elements predominantly in 3′-UTRs: RRM1/2 provide the primary RNA-binding surface, while RRM3 mediates dimerization/multimerization through its α-helical face and contributes additional RNA contacts, with both activities required for target mRNA regulation (PMID:30418581, PMID:28790173). Signal-dependent post-translational modifications—including Cdk1/AMPK-regulated phosphorylation at S242, JAK3 phosphorylation at Y200, CARM1-mediated methylation at R217, and PKC-driven phosphorylation—govern CRM1-dependent nuclear export, stress-granule recruitment, and the breadth of cytoplasmic mRNA targets, while caspase cleavage during apoptosis generates a fragment that sequesters transportin-2 and traps HuR in the cytoplasm (PMID:18948743, PMID:24106086, PMID:30016500, PMID:21646354). In the cytoplasm, HuR stabilizes proliferative (cyclin A/B1), anti-apoptotic (XIAP, ProTα), metabolic (ATGL, GLS), and cardiac (SCN5A) transcripts while also enhancing cap-independent (XIAP IRES) and cap-dependent translation, and it antagonizes miRNA-mediated silencing by oligomerizing along RNA to displace miRISC; competing noncoding RNAs—including lncRNAs (OIP5-AS1, LINC00941), circRNAs (circPABPN1, circAGO2, circDLC1, circTICRR), vtRNA2-1, and 7SL—act as molecular sponges that titrate HuR away from target mRNAs (PMID:10811625, PMID:15861128, PMID:21102524, PMID:22362743, PMID:26819413, PMID:31924774, PMID:29454929, PMID:38965208).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Establishing HuR as a cell-cycle mRNA stabilizer answered how AU-rich–element transcripts escape rapid decay during S/G2: HuR binds cyclin A and B1 3′-UTRs in a cell-cycle-dependent manner, and its depletion shortens their half-lives and impairs proliferation.

    Evidence Gel-shift, supershift, mRNA half-life measurements, antisense HuR knockdown in synchronized RKO cells

    PMID:10811625

    Open questions at the time
    • Identity of the kinase(s) controlling cell-cycle-dependent HuR-RNA association was unknown
    • No structural basis for selective cyclin mRNA recognition
  2. 2002 High

    Identifying AMPK as a regulator of HuR nucleocytoplasmic distribution revealed a metabolic checkpoint over HuR activity: AMPK activation retains HuR in the nucleus and destabilizes p21/cyclin mRNAs, while AMPK inhibition increases cytoplasmic HuR and target mRNA stability.

    Evidence Dominant-negative and constitutively active AMPK adenoviruses, cell fractionation, RIP, mRNA half-life measurements

    PMID:11971974

    Open questions at the time
    • Direct phosphorylation site on HuR by AMPK not mapped
    • Relationship between AMPK and CRM1-mediated export undefined
  3. 2005 High

    Demonstrating that HuR enhances ProTα translation on polysomes after UV irradiation established HuR as a translational activator—not solely a stability factor—and linked this to an anti-apoptotic program.

    Evidence Polysome fractionation, chimeric mRNA reporter, HuR overexpression/RNAi in HeLa, ProTα antisense blockade

    PMID:15861128

    Open questions at the time
    • Mechanism by which HuR promotes polysome loading not defined
    • Whether HuR acts as a general IRES trans-acting factor unclear
  4. 2008 High

    Mapping S242 as a key phospho-switch in the HuR hinge domain resolved how a single residue controls cytoplasmic accumulation: S242A is constitutively cytoplasmic and hyper-stabilizes cyclin mRNAs, while S242D is nuclear-retained.

    Evidence Systematic Ser→Ala mutagenesis, cell fractionation, RIP, mRNA half-life, proliferation assays in HeLa

    PMID:18948743

    Open questions at the time
    • The kinase phosphorylating S242 in vivo was not identified in this study
    • In vivo physiological relevance not tested
  5. 2010 High

    Showing that HuR stimulates XIAP IRES-mediated translation and that HuR-dependent cytoprotection requires XIAP expression established a second translational target and a key node in the anti-apoptotic circuit.

    Evidence In vitro RNA binding, RIP, polysome profiling, functional epistasis in etoposide-treated cells

    PMID:21102524

    Open questions at the time
    • Structural basis of IRES recognition by HuR unknown
    • Whether HuR acts on other IRES elements systematically untested
  6. 2011 Medium

    Discovering that caspase cleavage of HuR generates a fragment that sequesters transportin-2 and blocks HuR nuclear re-import explained how apoptosis feeds forward to amplify cytoplasmic HuR accumulation.

    Evidence Co-IP of HuR–TRN2, caspase cleavage assays, TRN2 overexpression/knockdown with cell death readout

    PMID:21646354

    Open questions at the time
    • Caspase cleavage site not fully mapped
    • Relative contribution versus phosphorylation-driven export unclear
    • Single lab, awaits independent confirmation
  7. 2012 High

    In vitro reconstitution with purified miRISC and recombinant HuR revealed a direct competition mechanism: HuR oligomerizes along RNA and physically displaces miRISC even from distal sites, also blocking miRNA-guided deadenylation, establishing HuR as a general antagonist of miRNA silencing.

    Evidence Purified miRISC + recombinant HuR reconstitution, oligomerization mutants, deadenylation assay in Krebs-2 extract

    PMID:22362743

    Open questions at the time
    • Stoichiometry and kinetics of oligomerization in cells unknown
    • Whether all HuR targets benefit from miRISC displacement not tested
  8. 2013 High

    Identification of JAK3 phosphorylation at Y200 as a signal that prevents HuR stress-granule localization and accelerates SIRT1/VHL mRNA decay showed that distinct phospho-sites route HuR to different cytoplasmic compartments with opposing mRNA-fate outcomes.

    Evidence In vitro kinase assay, Y200F mutagenesis, RIP, stress granule imaging, mRNA decay assays

    PMID:24106086

    Open questions at the time
    • Structural mechanism linking Y200 phosphorylation to stress-granule exclusion unknown
    • Interplay between Y200 and S242 phosphorylation unexplored
  9. 2014 High

    The finding that ncRNA 7SL competes with HuR for TP53 mRNA binding, and that 7SL silencing increases p53 production, introduced the concept that non-coding RNAs can act as HuR sponges to modulate specific target outputs.

    Evidence RNA–protein interaction assays, polysome profiling, nascent translation, 7SL siRNA, RIP

    PMID:25123665

    Open questions at the time
    • Generality of ncRNA-sponge mechanism for other HuR targets unknown at this point
    • In vivo validation lacking
  10. 2016 High

    Discovery of OIP5-AS1 lncRNA as a HuR sponge that sequesters HuR away from proliferative mRNAs, and of HuR-mediated CRM1-dependent nuclear export of RMRP lncRNA, broadened HuR's role to include regulation of lncRNA trafficking and availability.

    Evidence MS2-tagged RNA pull-down, RIP, mRNA stability assays (OIP5-AS1); affinity pull-down + MS, CRM1 inhibition, fractionation (RMRP)

    PMID:26819413 PMID:27198227

    Open questions at the time
    • How HuR selects lncRNA cargoes for export versus sponging is unknown
    • Whether RMRP export is a direct CRM1-HuR co-export complex not resolved structurally
  11. 2018 High

    Dual post-translational modification mapping—R217 methylation by CARM1 and S221 dephosphorylation by PP2A—controlling HuR–CRM1 interaction strength provided a unified mechanism linking SAM metabolism and phosphatase tone to HuR subcellular localization and downstream neuronal gene programs.

    Evidence Co-IP of HuR–CRM1, methylation/phosphorylation analysis, siPpp2ca rescue, okadaic acid, Cd320 KO mice, patient fibroblasts

    PMID:30016500

    Open questions at the time
    • Structural basis of methylation-dependent CRM1 recognition unknown
    • Crosstalk with other HuR phospho-sites (S242, Y200) not examined
  12. 2019 High

    Crystallographic and NMR/SAXS analysis of full-length HuR revealed that all three RRMs are flexibly connected in the apo state but compact upon RNA binding, with RRM3 mediating dimerization through its α-helical face; disruption of either RRM3 dimerization or its RNA contacts abolished mRNA regulation in cells.

    Evidence Crystal structures (RRM3 free and RNA-bound), NMR, SAXS, mutagenesis, in vitro binding, mRNA stability in cells

    PMID:30418581

    Open questions at the time
    • No full-length HuR–RNA co-crystal structure
    • How oligomerization beyond dimer is organized on long mRNAs unclear
  13. 2019 High

    Adipose-specific HuR knockout mice demonstrated that HuR controls systemic metabolic homeostasis by stabilizing ATGL mRNA and promoting its translation; loss leads to obesity, glucose intolerance, and insulin resistance, establishing a tissue-level metabolic role.

    Evidence Adipose-specific KO mice, RIP, mRNA stability assays, polysome profiling, metabolic phenotyping

    PMID:31147543

    Open questions at the time
    • Full inventory of HuR-regulated lipid metabolism transcripts in adipose not defined
    • Whether HuR directly senses nutritional cues unclear
  14. 2020 High

    Transcriptome-wide mRNA stability analysis in fat-specific HuR KO mice showed HuR modulates hundreds of adipocyte transcripts including Insig1, revealing HuR as a broad repressor of adipogenesis whose loss causes adipocyte hypertrophy and glucose intolerance.

    Evidence Adipose-specific KO, transcriptome-wide stability analysis, primary adipocyte culture KD/OE, metabolic phenotyping

    PMID:31924774

    Open questions at the time
    • Whether HuR-mediated destabilization of some transcripts (e.g. Insig1) involves recruited decay factors not determined
    • Adipose-specific versus systemic contributions incompletely separated
  15. 2020 Medium

    Multiple noncoding RNA sponges—circPABPN1 blocking HuR–Atg16l1 mRNA interaction, circAGO2 enhancing HuR activity, circDLC1 competing for HuR–MMP1 binding—established circular RNAs as a pervasive regulatory layer modulating HuR target selectivity in autophagy and cancer.

    Evidence RIP, conditional intestinal KO mice (circPABPN1); RIP + co-IP + inhibitory peptide + xenograft (circAGO2); RIP + pull-down (circDLC1)

    PMID:30341421 PMID:31932481 PMID:33391541

    Open questions at the time
    • Quantitative stoichiometry of circRNA–HuR competition in physiological settings unknown
    • Most circRNA-HuR studies from single labs
    • Endogenous circRNA expression levels versus HuR abundance not compared
  16. 2022 Medium

    HuR regulates GLS alternative splicing and isoform-specific translation in breast cancer, altering glutamine anaplerosis; and HuR binds the 5′-UTR of Raptor mRNA in complex with eIF3a to control mTORC1 activity, expanding HuR's metabolic regulatory reach to include splicing and 5′-UTR translational control.

    Evidence siRNA KD + isoform quantification + metabolic flux (GLS); co-IP + RNA binding + mTOR activity (eIF3a-Raptor)

    PMID:35279705 PMID:38965208

    Open questions at the time
    • Mechanism by which HuR influences splice-site selection not defined
    • Whether eIF3a-HuR co-binding of 5′-UTRs is a general mechanism unknown
    • Each finding from single labs
  17. 2023 High

    Engineering of a TRIM21-based bioPROTAC using a nanobody that blocks HuR-RNA binding and degrades endogenous HuR provided tool-compound validation that acute, complete HuR depletion reverses tumor-promoting transcriptomic programs in vivo.

    Evidence VHH selection, TRIM21-bioPROTAC, in vitro HuR-RNA inhibition, proteomic analysis, xenograft model

    PMID:37925433

    Open questions at the time
    • Long-term in vivo safety/toxicity of HuR degradation not evaluated
    • Whether HuR family members compensate after chronic depletion unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length HuR–RNA co-crystal structure, a systems-level quantitative model integrating the contributions of competing ncRNA sponges, PTM crosstalk among phospho/methyl sites, and the in vivo therapeutic window for HuR inhibition remain unresolved.
  • No atomic-resolution structure of full-length HuR bound to a physiological mRNA target
  • Quantitative integration of multiple ncRNA sponges competing for limited HuR pools not modeled
  • Therapeutic index for systemic HuR inhibition in humans unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 15 GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3
Localization
GO:0005829 cytosol 6 GO:0005634 nucleus 5
Pathway
R-HSA-8953854 Metabolism of RNA 12 R-HSA-392499 Metabolism of proteins 7 R-HSA-5357801 Programmed Cell Death 6 R-HSA-9612973 Autophagy 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3
Partners
AUF1CARM1EIF3ATRN2XPO1

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 HuR directly binds mRNAs encoding cyclins A and B1 via their 3'-UTRs in a cell cycle-dependent manner, stabilizing these transcripts during S and G2 phases and promoting cell proliferation; reduced HuR expression decreased cyclin mRNA half-lives and impaired cell growth. Gel-shift assays, anti-HuR antibody supershift, mRNA half-life measurements, antisense HuR knockdown in synchronized RKO cells The EMBO journal High 10811625
2002 AMP-activated kinase (AMPK) regulates cytoplasmic HuR levels; AMPK inhibition increases cytoplasmic HuR and enhances HuR binding to p21, cyclin B1, and cyclin A mRNAs, elevating their expression and half-lives, while AMPK activation reduces cytoplasmic HuR and destabilizes these transcripts. Dominant-negative and constitutively active AMPK adenovirus infection, cell fractionation, RIP assays, mRNA half-life measurements Molecular and cellular biology High 11971974
2005 HuR binds the 3'-UTR of prothymosin alpha (ProTα) mRNA, promotes its cytoplasmic accumulation and translation onto heavier polysomes following UVC-induced apoptosis, and thereby exerts an antiapoptotic effect that is dependent on ProTα expression. Polysome fractionation, chimeric mRNA reporter assays, HuR overexpression and RNAi knockdown in HeLa cells, anti-sense oligomer blockade of ProTα translation The EMBO journal High 15861128
2008 Phosphorylation of HuR at serine 242 (S242) restricts its cytoplasmic localization; the S242A non-phosphorylatable mutant accumulates in the cytoplasm, increases association with cyclin A2 and cyclin B1 mRNAs, elevates their stability, and heightens cell proliferation, while the phosphomimetic S242D mutant remains nuclear. Systematic serine-to-alanine mutagenesis in HuR hinge domain, cell fractionation, RIP assays, mRNA half-life assays, proliferation measurements in HeLa cells Cell cycle High 18948743
2010 HuR stimulates translation of XIAP mRNA through the XIAP IRES; HuR binds XIAP IRES in vitro and in vivo, promotes recruitment of XIAP mRNA into polysomes, and HuR-mediated cytoprotection against etoposide requires XIAP expression. In vitro RNA binding assay, RIP, polysome profiling, HuR overexpression with XIAP requirement validation in apoptosis assay Oncogene High 21102524
2010 PKCβ activation in diabetic retinas leads to phosphorylation/activation of HuR, which then binds VEGF mRNA (detected by immunoprecipitation coupled to RT-PCR), resulting in enhanced VEGF protein expression; PKCβ inhibition blocks this pathway. Immunoprecipitation-coupled RT-PCR (RNP-IP), HuR phosphorylation detection, PKCβ inhibitor treatment in STZ-diabetic rats Biochemical pharmacology Medium 20599775
2011 HuR interacts with the nucleolin (NCL) 3'-UTR and specifically promotes nucleolin translation (without affecting mRNA levels); HuR silencing mobilizes NCL RNA to processing bodies. miR-494 competitively inhibits nucleolin expression and competes with HuR for modulation of nucleolin translation. MS2-tagged NCL 3'-UTR pull-down, RIP, polysome profiling, processing body imaging, miRNA mimic/inhibitor experiments in HeLa cells Molecular and cellular biology High 21859890
2012 HuR relieves miRNA-mediated repression by promoting dissociation of miRISC from target RNA; using purified miRISC and recombinant HuR, HuR oligomerization along RNA causes miRISC displacement even when binding sites are distal, and HuR also inhibits miRNA-mediated mRNA deadenylation. In vitro reconstitution with purified miRISC and recombinant HuR, HuR oligomerization mutants, deadenylation assay in Krebs-2 ascites extract Nucleic acids research High 22362743
2012 HuR and AUF1 bind overlapping U-rich, single-stranded sequences in the 3'-UTR of target mRNAs (androgen receptor mRNA and MTA1 mRNA); defining features of HuR binding sites are U-richness and single-strandedness. In vitro RNA binding analysis using radiolabeled transcripts and recombinant proteins, competition assays Journal of biochemistry Medium 22368252
2012 During alphavirus (Sindbis virus) infection, HuR undergoes dephosphorylation and relocalizes from the nucleus to the cytoplasm; this relocalization requires viral gene expression, is distinct from stress-induced relocalization, and is not a general response to viral infection. Cell fractionation, phosphorylation state analysis, viral infection of multiple mammalian cell types with multiple alphavirus strains The Journal of biological chemistry Medium 22915590
2013 JAK3 phosphorylates HuR at tyrosine 200, which prevents HuR localization to stress granules, reduces HuR interaction with SIRT1 and VHL mRNAs, and accelerates their decay; menadione activates JAK3 to trigger this phosphorylation. In vitro kinase assay, site-directed mutagenesis (Y200F), RIP, stress granule immunofluorescence, mRNA decay assays Nucleic acids research High 24106086
2014 The ncRNA 7SL forms a partial hybrid with the 3'-UTR of TP53 mRNA, reducing p53 translation; 7SL competes with HuR for binding to TP53 mRNA, and silencing 7SL increases HuR-TP53 mRNA interaction and p53 abundance. RNA-protein interaction assays, polysome profiling, nascent translation assays, 7SL siRNA knockdown, RIP Nucleic acids research High 25123665
2016 HuR binds RMRP lncRNA in the nucleus and mediates its CRM1-dependent nuclear export to the cytosol; after RMRP is imported into mitochondria, GRSF1 binds and stabilizes it. Loss of GRSF1 reduces mitochondrial RMRP and suppresses oxygen consumption and mitochondrial DNA replication priming. Affinity RNA pull-down followed by mass spectrometry, CRM1 inhibition (leptomycin B), cell fractionation, mitochondrial oxygen consumption assays, GRSF1 knockdown Genes & development High 27198227
2016 OIP5-AS1 lncRNA acts as a competing endogenous RNA (sponge) for HuR: high OIP5-AS1 levels increase HuR-OIP5-AS1 complexes and prevent HuR interaction with target proliferative mRNAs, while HuR stabilizes OIP5-AS1; miR-424 competes with HuR for OIP5-AS1 binding. MS2-hairpin tagging of OIP5-AS1, RIP, mRNA stability assays, proliferation assays in HeLa cells Nucleic acids research High 26819413
2016 HuR cytoplasmic translocation is activated downstream of the Gq-p38 MAPK pathway in cardiomyocytes; HuR activation is necessary for Gq-mediated hypertrophic growth (measured by cell size and ANF expression), and HuR overexpression is sufficient to induce hypertrophy and modulates NFAT transcriptional activity. siRNA knockdown, HuR overexpression, pharmacological p38 and Gq inhibition, NFAT-luciferase reporter assay, cell size measurement in NRVMs Cellular signalling Medium 27521603
2017 HuR dimerization occurs through the α-helical face of RRM3; using split-luciferase and BRET assays plus site-directed mutagenesis, HuR multimerization (at least trimeric) was demonstrated in glioma cells, and disruption of multimerization with dihydrotanshinone-I or compound 5 reduces tumor cell survival. Split luciferase assay, bioluminescence resonance energy transfer (BRET), site-directed mutagenesis, pharmacological inhibition The Journal of biological chemistry Medium 28790173
2017 Dihydrotanshinone-I (DHTS) binds residues within RRM1 and RRM2 of HuR (identified by NMR titration and MD simulation), stabilizes HuR in a locked conformation that competitively blocks RNA binding, and preferentially inhibits HuR association with weaker mRNA targets transcriptome-wide. NMR titration, molecular dynamics simulation, RNA EMSA, AlphaScreen assay, RIP-chip (RIP + microarray), xenograft tumor growth assay Nucleic acids research High 28934484
2018 ELAVL1/HuR promotes ferroptosis in hepatic stellate cells by binding AU-rich elements in the 3'-UTR (F3 region) of BECN1 mRNA and stabilizing it, thereby promoting autophagy/ferritinophagy; ELAVL1 protein is stabilized upon ferroptosis induction through inhibition of the ubiquitin-proteasome pathway. RIP assays, BECN1 mRNA stability assays with internal deletion reporters, ELAVL1 siRNA/plasmid, autophagy flux assays, mouse hepatic stellate cell-specific ELAVL1 knockdown in fibrosis models Autophagy High 30081711
2018 Hypomethylation at R-217 (by decreased SAM/CARM1) and dephosphorylation at S221 (by increased PP2A) cause decreased interaction of ELAVL1/HuR with CRM1/exportin and cytoplasmic mislocalization in a cobalamin-deficiency model, leading to reduced SIRT1 expression and altered neuronal gene programs. Cell fractionation, co-immunoprecipitation of HuR-CRM1, methylation/phosphorylation analysis, siPpp2ca rescue, okadaic acid treatment, Cd320 knockout mice Nucleic acids research High 30016500
2018 CircAGO2 physically interacts with HuR protein and facilitates its activation and enrichment on the 3'-UTR of target genes, resulting in reduced AGO2 binding and repression of AGO2/miRNA-mediated gene silencing; blocking the circAGO2-HuR interaction with a cell-penetrating inhibitory peptide suppresses cancer cell tumorigenesis. RIP assays, co-immunoprecipitation, biotin-labeled RNA pull-down, cell-penetrating inhibitory peptide, xenograft models Cell death and differentiation Medium 30341421
2019 HuR RRM3 mediates canonical RNA interactions and dimerization through its α-helical face; all three RRMs are flexibly connected in full-length HuR absent RNA but adopt a compact arrangement when RNA-bound; RRM3 dimerization and RNA binding are required for HuR's ability to regulate target mRNA levels in human cells. Crystal structures of RRM3 free and RNA-bound, NMR, SAXS, mutagenesis, in vitro RNA binding assays, mRNA stability measurements in human cells Nucleic acids research High 30418581
2019 HuR positively regulates ATGL expression by binding ATGL mRNA and promoting both its stability and translation; adipose-specific HuR knockout mice show obesity with reduced ATGL expression, glucose intolerance, and insulin resistance on high-fat diet. Adipose-specific HuR knockout mice (HuRAKO), RIP, mRNA stability assays, polysome profiling, metabolic phenotyping Nature communications High 31147543
2019 WTAP-mediated m6A modification of ETS1 mRNA leads to post-transcriptional suppression of ETS1 expression, with HuR acting as an RNA stabilizer within this regulatory axis; m6A modification reduces ETS1 mRNA stability in an HuR-dependent manner in hepatocellular carcinoma cells. MeRIP assay, RIP assay, m6A dot blot, luciferase reporter, RNA sequencing Molecular cancer Medium 31438961
2011 Transportin 2 (TRN2) normally imports HuR into the nucleus; during apoptosis, caspase-mediated cleavage of cytoplasmic HuR generates a fragment that interacts with TRN2, blocking HuR re-import, concentrating HuR in the cytoplasm, and advancing apoptosis. Co-immunoprecipitation of HuR-TRN2, caspase cleavage assays, TRN2 overexpression/knockdown with cell death readout The Journal of biological chemistry Medium 21646354
2012 Insulin induces HuR translocation from nucleus to cytoplasm, increasing HuR binding to AT1R mRNA 3'-UTR, stabilizing AT1R mRNA and upregulating AT1R expression; inhibiting HuR translocation attenuates this insulin response. Affinity purification + mass spectrometry, RIP, cell fractionation, HuR overexpression/knockdown, mRNA stability assays Nucleic acids research High 22362742
2015 ECRG2 tumor suppressor promotes HuR ubiquitination and proteasomal degradation; ECRG2-mediated reduction of HuR decreases XIAP mRNA stability and expression, suppressing cancer cell growth; ECRG2 cancer mutant V30E fails to ubiquitinate/degrade HuR. Ubiquitination assay, mRNA stability assay, co-immunoprecipitation, site-directed mutagenesis (V30E), cell growth and apoptosis assays Oncogene Medium 26434587
2018 HuR binds SCN5A mRNA in cardiomyocytes, protecting it from decay; HuR expression is reduced in failing hearts; AAV9-mediated overexpression of HuR in infarcted mouse hearts rescues SCN5A expression, improves action potential upstroke velocity and conduction, and reduces reentrant arrhythmia risk. RIP, mRNA decay assays, AAV9 delivery, optical mapping of intact heart, myocardial infarction mouse model Heart rhythm High 29454929
2018 Loss of HuR during replicative senescence enhances TIN2 expression by releasing TIN2 mRNA from HuR-mediated destabilization; elevated TIN2 increases mitochondrial localization of TIN2, raises ROS levels, and contributes to senescence induction. RIP, mRNA stability assay, HuR depletion, mitochondrial fractionation, ROS measurement, senescence assays Nucleic acids research Medium 29584879
2020 HuR directly interacts with Atg16l1 mRNA 3'-UTR and enhances ATG16L1 translation without affecting mRNA stability; circPABPN1 blocks HuR binding to Atg16l1 mRNA and reduces ATG16L1 production, thereby inhibiting autophagy in intestinal epithelial cells. RIP, HuR conditional intestinal-specific knockout mice, ATG16L1 translation assay, circPABPN1 overexpression/knockdown, polysome profiling Molecular and cellular biology High 31932481
2020 AFP binds to HuR protein and increases accumulation of HuR in the cytoplasm, leading to inhibition of Fas mRNA translation and resistance to Fas/FADD-mediated apoptosis in HCC cells. Co-immunoprecipitation (AFP-HuR), cell fractionation, Fas mRNA translation assay, AFP knockdown in mouse and cell models Cell death & disease Medium 33009373
2020 HuR is a major repressor of adipogenesis; fat-specific HuR knockout enhances adipogenic gene programs, increases adipocyte hypertrophy, and causes systemic glucose intolerance. Mechanistically, HuR modulates the stability of hundreds of adipocyte transcripts including Insig1 mRNA. Adipose-specific HuR KO mice, primary adipocyte culture KD/OE, transcriptome-wide mRNA stability analysis, metabolic phenotyping Nature communications High 31924774
2020 HuR stabilizes PLB (phospholamban) mRNA and destabilizes β1-AR mRNA in cardiomyocytes; cardiomyocyte-specific HuR deletion mitigates isoproterenol-induced PLB upregulation and aggravates myocardial hypertrophy and fibrosis. Cardiomyocyte-specific HuR KO mice, RIP (HuR-PLB and HuR-β1-AR mRNA), mRNA stability assays, cardiac phenotyping Cardiovascular research Medium 31373621
2021 HuR binds the mRNAs of AMPKα1 and AMPKα2, increasing their stability and translation; smooth muscle-specific HuR knockout reduces p-AMPK and LC3II, increases p62, causing defective autophagy and increased atherosclerotic plaque burden. Smooth muscle-specific HuR KO mice, RIP, mRNA stability assays, autophagy flux assays, atherosclerosis model Cell death & disease Medium 33837179
2021 HuR stabilizes HOXC10 mRNA by physically interacting with the cytosine-rich stretch of the lncRNA HMS and the HOXC10 3'-UTR; HuR and HMS co-operatively maintain HOXC10 mRNA levels to support invasive cancer cell phenotypes. RNA pull-down, deletion mapping, RIP, 3'-UTR luciferase reporter assay, mRNA stability assay The Journal of biological chemistry Medium 34302808
2022 LINC00941/lncIAPF forms an RNA-protein complex with ELAVL1/HuR, and this complex inhibits autophagosome-lysosome fusion. The LINC00941-ELAVL1 complex controls the stability of EZH2, STAT1, and FOXK1 mRNAs to block autophagy and promote fibroblast-to-myofibroblast differentiation in pulmonary fibrosis. RNA affinity isolation, RIP, RNase-RIP, mRNA half-life analysis, ELAVL1 RIP-seq, dual-fluorescence autophagic flux assay, mouse fibrosis model Autophagy High 35427207
2022 vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thereby decreasing their translation and causing intestinal epithelial barrier dysfunction; elevated vtRNA2-1 in vivo increases gut barrier vulnerability to septic stress. RNA-protein interaction assays, RIP, translation assays (claudin 1 and occludin), vtRNA2-1 overexpression/knockdown in cells and intestinal organoids, in vivo sepsis model EMBO reports Medium 36440604
2022 HuR regulates GLS (glutaminase) mRNA alternative splicing and isoform translation/stability in breast cancer; ELAVL1 knockdown reduces KGA isoform and increases GAC, alters glutamine anaplerosis into TCA cycle, and drives glutamine dependence. ELAVL1 siRNA knockdown, isoform quantification, metabolic flux analysis, polysome profiling, cell growth/invasion assays Nature communications High 38965208
2022 eIF3a interacts with HuR, and the eIF3a-HuR complex binds to the 5'-UTR of Raptor mRNA to regulate its translation, thereby modulating mTORC1 kinase activity and cellular response to cisplatin. Co-immunoprecipitation (eIF3a-HuR), RNA-protein binding assay (5'-UTR of Raptor mRNA), Raptor translation assay, mTOR activity measurements Oncogene Medium 35279705
2023 A single-domain antibody (VHH) that binds HuR with low nanomolar affinity and inhibits HuR-RNA binding was used to engineer a TRIM21-based bioPROTAC; this bioPROTAC degrades endogenous HuR, reverses tumor-promoting properties in vivo by altering the HuR-regulated proteome. VHH antibody selection, TRIM21-bioPROTAC engineering, in vitro HuR-RNA inhibition assay, proteomic analysis, xenograft tumor model Nature communications High 37925433
2021 circDLC1 binds to HuR protein and reduces HuR-MMP1 mRNA interaction, thereby inhibiting MMP1 expression and suppressing hepatocellular carcinoma progression. RNA FISH, RIP assays, biotin-labeled RNA pull-down, RNA-seq Theranostics Medium 33391541
2022 circTICRR interacts with HuR protein via binding to F287/F289 in the RRM3 domain, stabilizing GLUD1 mRNA and elevating GLUD1 protein, thereby suppressing autophagy and promoting cervical cancer progression; an inhibitory peptide targeting this interaction promotes autophagy and apoptosis. Co-immunoprecipitation, RIP, site-directed mutagenesis (F287A/F289A in RRM3), inhibitory peptide, xenograft models Cell death & disease Medium 35595754
2022 HuR binds ARID1A mRNA and increases its stability in breast cancer cells; ARID1A suppresses radiation-induced DNA double-strand breaks, and ARID1A overexpression rescues the loss of radioresistance triggered by HuR inhibition, demonstrating an HuR-ARID1A axis in radiation resistance. RIP, mRNA stability assay, γH2AX foci (DNA DSB measurement), ARID1A rescue experiment, HuR inhibitor Cancers Medium 31847141
2022 HuR promotes SOD2 mRNA translation (not stability) in response to matrix detachment; anchorage-independence induces cytosolic HuR accumulation and HuR-SOD2 mRNA binding via p38 MAPK activation; HuR siRNA knockdown prevents increased SOD2 mRNA association with heavy polysomes and reduces nascent SOD2 synthesis. Polyribosome profiling, RIP, HuR siRNA, p38 inhibition, cytosol/nuclear fractionation, nascent protein synthesis assay Redox biology High 35594792
2021 S-adenosylmethionine (SAM) concentration determines HuR subcellular localization via protein methylation; HuR directly binds ATRAP mRNA and controls its nucleocytoplasmic shuttling, with SAM supplementation upregulating ATRAP protein expression through maintaining HuR nuclear export. Cell fractionation, RIP, SAM supplementation/depletion, methylation analysis, HFD rat and OA-treated cell models Cell death & disease Medium 33753727
2015 HuR binds to AU-rich element-containing mRNAs and directly suppresses Fas mRNA translation via two AU-rich domains in the Fas 3'-UTR; HuR silencing increases cell-surface Fas and sensitizes HCC cells to FasL-induced apoptosis, and in vivo HuR overexpression in mouse liver downregulates Fas. RIP, dual luciferase reporter assay (Fas 3'-UTR), HuR siRNA, hydrodynamic transfection in mice, Fas surface expression by flow cytometry Molecular cancer research High 25678597
2014 HSF1 regulates HuR expression levels, and HuR in turn controls β-catenin translation in mammary cells; mTOR phosphorylation of HSF1-S326 maintains this axis, with mTOR knockdown decreasing β-catenin through a HuR-dependent mechanism. HSF1 gain/loss of function, HuR siRNA, β-catenin translation assays, mTOR siRNA, phospho-HSF1 (S326) analysis Oncogene Medium 24954509

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1. Molecular cancer 522 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 390 30081711
2010 Posttranscriptional regulation of cancer traits by HuR. Wiley interdisciplinary reviews. RNA 352 21935886
2003 Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 255 14562043
2018 Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes. Cell death and differentiation 246 30341421
2007 Posttranscriptional orchestration of an anti-apoptotic program by HuR. Cell cycle (Georgetown, Tex.) 211 17534146
2016 Posttranslational control of HuR function. Wiley interdisciplinary reviews. RNA 210 27307117
2016 HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes & development 191 27198227
2002 AMP-activated kinase regulates cytoplasmic HuR. Molecular and cellular biology 187 11971974
2005 Antiapoptotic function of RNA-binding protein HuR effected through prothymosin alpha. The EMBO journal 150 15861128
2016 LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR. Nucleic acids research 149 26819413
2021 Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR. Theranostics 146 33391541
2016 HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer. Cancer medicine 146 27075229
2012 HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA. Nucleic acids research 145 22362743
2019 LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis. Molecular cancer 144 31752906
2015 Identification and validation of novel small molecule disruptors of HuR-mRNA interaction. ACS chemical biology 131 25750985
2020 AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway. Cell death & disease 126 33009373
2014 7SL RNA represses p53 translation by competing with HuR. Nucleic acids research 118 25123665
2018 The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer. Molecular cancer 104 29351796
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
2014 HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 87 24954509
2022 ATF3 -activated accelerating effect of LINC00941/lncIAPF on fibroblast-to-myofibroblast differentiation by blocking autophagy depending on ELAVL1/HuR in pulmonary fibrosis. Autophagy 85 35427207
2022 HuR as a molecular target for cancer therapeutics and immune-related disorders. Advanced drug delivery reviews 82 35817212
2020 The RNA-binding protein HuR is a negative regulator in adipogenesis. Nature communications 82 31924774
2019 HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs. Nucleic acids research 81 30418581
2017 Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic acids research 79 28934484
2020 Interaction between HuR and circPABPN1 Modulates Autophagy in the Intestinal Epithelium by Altering ATG16L1 Translation. Molecular and cellular biology 77 31932481
2010 RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation. Oncogene 77 21102524
2017 HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis. Cancer research 76 28428272
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 LncRNA BBOX1-AS1 upregulates HOXC6 expression through miR-361-3p and HuR to drive cervical cancer progression. Cell proliferation 65 32515533
2010 Cytoplasmic HuR expression correlates with angiogenesis, lymphangiogenesis, and poor outcome in lung cancer. Medical oncology (Northwood, London, England) 64 21046284
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
2010 HuR regulates beta-tubulin isotype expression in ovarian cancer. Cancer research 57 20587520
2012 Sequence requirements for RNA binding by HuR and AUF1. Journal of biochemistry 55 22368252
2023 Targeting the RNA-Binding Protein HuR in Cancer. Cancer research 54 37683260
2014 Neuroprotection requires the functions of the RNA-binding protein HuR. Cell death and differentiation 54 25301069
2018 The AU-rich element landscape across human transcriptome reveals a large proportion in introns and regulation by ELAVL1/HuR. Biochimica et biophysica acta. Gene regulatory mechanisms 53 29413897
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
2012 Dephosphorylation of HuR protein during alphavirus infection is associated with HuR relocalization to the cytoplasm. The Journal of biological chemistry 50 22915590
2020 HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. The Journal of clinical investigation 48 32315290
2019 The RNA Binding Protein HuR: A Promising Drug Target for Anticancer Therapy. Current cancer drug targets 48 30381077
2013 Tyrosine phosphorylation of HuR by JAK3 triggers dissociation and degradation of HuR target mRNAs. Nucleic acids research 48 24106086
2017 HuR promotes breast cancer cell proliferation and survival via binding to CDK3 mRNA. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 28501005
2019 Abemaciclib Is Effective Against Pancreatic Cancer Cells and Synergizes with HuR and YAP1 Inhibition. Molecular cancer research : MCR 46 31383722
2017 Hu antigen R (HuR) multimerization contributes to glioma disease progression. The Journal of biological chemistry 46 28790173
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
2009 Cytoplasmic expression of HuR is related to cyclooxygenase-2 expression in colon cancer. Cancer research and treatment 46 19707506
2017 CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype. Molecular cancer research : MCR 45 28242812
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 41 29584879
2016 Activation of HuR downstream of p38 MAPK promotes cardiomyocyte hypertrophy. Cellular signalling 41 27521603
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
1997 Localization of the human HuR gene to chromosome 19p13.2. Human genetics 37 9003489
2015 MicroRNA-16 modulates HuR regulation of cyclin E1 in breast cancer cells. International journal of molecular sciences 36 25830480
2014 Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis. Current opinion in hematology 36 24714527
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
2022 N6-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex. Cell death and differentiation 33 35871232
2019 RETRACTED: lncRNA RMST Enhances DNMT3 Expression through Interaction with HuR. Molecular therapy : the journal of the American Society of Gene Therapy 32 31636039
2017 Emerging role of HuR in inflammatory response in kidney diseases. Acta biochimica et biophysica Sinica 32 28910975
2023 A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation. Nature communications 30 37925433
2022 Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer. Cell death & disease 30 35595754
2021 Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors. Cancer research 30 33602784
2019 HuR interacts with lincBRN1a and lincBRN1b during neuronal stem cells differentiation. RNA biology 29 31345103
2018 Inherited disorders of cobalamin metabolism disrupt nucleocytoplasmic transport of mRNA through impaired methylation/phosphorylation of ELAVL1/HuR. Nucleic acids research 29 30016500
2015 Negative regulation of RNA-binding protein HuR by tumor-suppressor ECRG2. Oncogene 29 26434587
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
2023 m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR. Molecular cancer research : MCR 25 37647111
2021 Drug delivery approaches for HuR-targeted therapy for lung cancer. Advanced drug delivery reviews 24 34822926
2018 HuR-mediated SCN5A messenger RNA stability reduces arrhythmic risk in heart failure. Heart rhythm 24 29454929
2017 Transcriptome-wide Identification and Validation of Interactions between the miRNA Machinery and HuR on mRNA Targets. Journal of molecular biology 24 29273203
2012 Regulation of AT1R expression through HuR by insulin. Nucleic acids research 24 22362742
2020 Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR. Human cell 22 32951177
2017 Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18. Cancer research and treatment 22 28231690
2015 Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation. Nucleic acids research 22 26490963
2014 Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1. Oncotarget 22 25526033
2023 LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis. Cell death & disease 21 36849492
2022 Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors. Cancers 21 35681645
2022 eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage. Oncogene 20 35279705
2022 CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA. Cell death discovery 20 35568705
2022 Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR. EMBO reports 20 36440604
2020 HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth. Cancers 20 32455577
2011 Transportin 2 regulates apoptosis through the RNA-binding protein HuR. The Journal of biological chemistry 20 21646354
2022 HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence. Redox biology 19 35594792
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
2020 HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability. Cell biochemistry and biophysics 18 32901414
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