Affinage

HNRNPD

Heterogeneous nuclear ribonucleoprotein D0 · UniProt Q14103

Length
355 aa
Mass
38.4 kDa
Annotated
2026-04-28
100 papers in source corpus 50 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPD (AUF1) is a central post-transcriptional regulator that controls mRNA turnover, translation, and genome maintenance through isoform-specific RNA- and DNA-binding activities. Its four alternatively spliced isoforms (p37, p40, p42, p45) assemble as dimers and tetramers on U-/GU-rich and AU-rich elements in target mRNA 3′-UTRs, recruiting a multisubunit decay complex containing eIF4G, PABP, Hsp70, Hsp27, and the exosome to direct ARE-mediated mRNA degradation—critically attenuating inflammatory cytokine (TNFα, IL-1β) expression, as demonstrated by the lethal endotoxic shock phenotype of AUF1-knockout mice (PMID:17085481, PMID:18573886, PMID:16556936). AUF1 isoform abundance is controlled by ubiquitin-dependent proteasomal degradation via β-TrCP and FBXW7 E3 ligases, regulated by p38/Hsp27 and PKC-dependent phosphorylation, and modulated by PRMT1-mediated arginine methylation; these post-translational modifications dictate whether AUF1 destabilizes, stabilizes, or translationally activates specific targets such as MYC, p21, DNMT1, and CRY1 mRNAs (PMID:23530064, PMID:35391558, PMID:27520967, PMID:17486099, PMID:24423872). Beyond mRNA decay, AUF1 activates TERT transcription to maintain telomere integrity, facilitates AGO2–miRNA loading, suppresses miRNA biogenesis by destabilizing DICER1 mRNA, functions as an RNA chaperone enabling flavivirus genome cyclization, and prevents pathological R-loop accumulation at DNA double-strand breaks to support homologous recombination repair (PMID:22633954, PMID:28334781, PMID:23066106, PMID:25078689, PMID:30799487).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Defining AUF1's dual role in mRNA stability: identification as a component of the α-globin mRNA stabilization complex and demonstration that its ARE-binding complex formation is phosphorylation-dependent established that AUF1 can both stabilize and destabilize mRNAs depending on context.

    Evidence Yeast two-hybrid, co-IP, gel-shift with kinase inhibitors in monocytes

    PMID:9199324 PMID:9234743

    Open questions at the time
    • Kinase(s) phosphorylating AUF1 in monocytes not identified
    • Structural basis of dual stabilizing vs. destabilizing function unknown
  2. 1999 High

    Biochemical reconstitution of AUF1 oligomerization on AREs revealed sequential dimer-to-tetramer assembly, mapped RNA-binding to both RRMs plus flanking domains, and demonstrated AUF1 is a limiting factor for ARE-mRNA decay that can bypass the translation-dependent step.

    Evidence Chemical cross-linking, fluorescence anisotropy, deletion mutagenesis, cell-free mRNA decay with immunodepletion, isoform overexpression

    PMID:10559216 PMID:10567360 PMID:12944492 PMID:9346902

    Open questions at the time
    • Structure of oligomeric AUF1-ARE complex not solved
    • How AUF1 bypasses translation-dependent decay step mechanistically unclear
  3. 2002 High

    Discovery that exon 7 governs isoform-specific ubiquitination (p37/p40 ubiquitinated, p42/p45 protected) and identification of LDH as a polysome-associated AUF1 complex subunit established that AUF1 turnover and complex composition are isoform-determined.

    Evidence In vitro ubiquitination assay with exon 7 deletion mutants, polysome fractionation with purified protein co-IP

    PMID:12107167 PMID:12136087

    Open questions at the time
    • E3 ligase responsible for ubiquitination not yet identified at this stage
    • Full subunit composition of polysomal AUF1 complex unknown
  4. 2003 High

    Mapping nucleocytoplasmic shuttling signals and phosphorylation sites (Ser83/Ser87 on p40) showed that isoform-specific subcellular distribution and signal-dependent phosphorylation directly control ARE-binding activity and target mRNA half-life.

    Evidence Heterokaryon shuttling, GFP fusions, phosphopeptide mapping on polysome fractions, TPA treatment

    PMID:12668672 PMID:12819195

    Open questions at the time
    • Kinase(s) for Ser83/Ser87 not definitively identified
    • Mechanism linking nuclear export to mRNA decay not resolved
  5. 2004 High

    Demonstration that HuR and AUF1 compete for common ARE sites in the cytoplasm while coexisting in nuclear RNPs, and that relative isoform ratios rather than total AUF1 levels determine mRNA fate, reframed AUF1 function as a combinatorial, isoform-ratio-dependent system.

    Evidence Co-IP with subcellular fractionation, isoform-selective siRNA knockdown with ARE reporter and GM-CSF readout

    PMID:14976220 PMID:15257295

    Open questions at the time
    • How isoform ratios are set in different tissues unclear
    • Whether HuR-AUF1 competition is direct or involves intermediary factors
  6. 2006 High

    Reconstitution of AUF1 interactions with eIF4G and PABP, the AUF1-knockout mouse endotoxic shock phenotype, and linkage of AUF1 mRNA autoregulation to NMD collectively established AUF1 as a central, physiologically essential mediator of cytokine mRNA decay with self-limiting expression.

    Evidence Purified protein binding assays, AUF1 KO mouse with endotoxin challenge, Upf1/Upf2 RNAi with AUF1 mRNA variant analysis

    PMID:16556936 PMID:17000771 PMID:17030625 PMID:17085481

    Open questions at the time
    • How AUF1 hands off ARE-mRNAs to the exosome mechanistically unclear
    • Tissue-specific requirements for individual isoforms not systematically mapped
  7. 2008 High

    Identification of Hsp27 as a functional ASTRC subunit and the inflammatory dermatitis phenotype of AUF1-KO mice extended AUF1's role to immune homeostasis, while NuRD complex interactions revealed an unexpected chromatin-regulatory function.

    Evidence Co-IP and siRNA for Hsp27, KO mouse histology and cytokine profiling, co-IP with HDAC1/MTA2

    PMID:18413351 PMID:18573886 PMID:18830269

    Open questions at the time
    • Chromatin-level function of AUF1 mechanistically underdeveloped
    • Whether NuRD interaction is RNA-dependent unknown
  8. 2011 High

    Mapping the p38–MK2–Hsp27 axis to AUF1 proteasomal destruction identified the signaling logic by which inflammatory stimuli stabilize cytokine mRNAs: signal-induced Hsp27 phosphorylation drives AUF1 degradation, relieving ARE-mRNA decay.

    Evidence Hsp27 phosphomimetic mutants with proteasome inhibition and mRNA stability assays

    PMID:21245386

    Open questions at the time
    • Whether other E3 ligases besides SCF-β-TrCP participate not yet tested
  9. 2012 High

    Discovery that AUF1 activates TERT transcription and that AUF1-KO mice undergo telomere erosion and premature aging, combined with suppression of DICER1 mRNA stability, revealed AUF1's role in both telomere maintenance and global miRNA biogenesis regulation.

    Evidence AUF1 KO mouse telomere analysis with rescue, TERT promoter binding, DICER1 RIP and mRNA half-life upon AUF1 knockdown/overexpression

    PMID:22633954 PMID:23066106

    Open questions at the time
    • How AUF1 switches from RNA-binding to DNA-binding (TERT promoter) mode unclear
    • In vivo miRNA profile changes in AUF1-KO not fully characterized
  10. 2013 High

    Identification of β-TrCP as the E3 ligase for AUF1 ubiquitination, requiring Hsp27 phosphorylation, completed the signaling circuit controlling AUF1 protein levels; antiviral roles against poliovirus and CVB3 broadened AUF1 function beyond host mRNA decay.

    Evidence β-TrCP siRNA/overexpression with ubiquitination assays; viral binding assays and replication readouts for PV/CVB3

    PMID:23530064 PMID:23572232 PMID:23903828

    Open questions at the time
    • Degron motif on AUF1 recognized by β-TrCP not mapped
    • Whether antiviral activity operates through ARE-mRNA decay machinery or independently unclear
  11. 2014 High

    Transcriptome-wide PAR-CLIP defined AUF1's primary binding signature as U-/GU-rich sequences, revealed regulation of noncoding RNA (NEAT1/paraspeckles), and uncovered RNA quality control (8-oxoG RNA clearance), RNA chaperone activity for flavivirus replication, and cooperative enhancement of TTP-family ARE binding.

    Evidence PAR-CLIP with ribosome profiling, AUF1-KO oxidized RNA quantification, in vitro WNV RNA cyclization, FRET with purified AUF1-TTP

    PMID:22203679 PMID:25078689 PMID:25366541 PMID:25486179

    Open questions at the time
    • Full structural basis for RNA chaperone vs. decay function not distinguished
    • Whether 8-oxoG RNA selectivity involves a specific binding pocket unknown
  12. 2017 High

    Single-molecule and global analyses showed AUF1 facilitates AGO2–miRNA loading, establishing a mechanistic intersection between AUF1 and the miRNA silencing pathway beyond DICER1 mRNA regulation.

    Evidence AGO2 RIP upon AUF1 depletion, single-molecule FRET of AGO2–let-7b–mRNA assembly

    PMID:28334781

    Open questions at the time
    • Which AUF1 isoform(s) mediate AGO2 loading not resolved
    • Whether AUF1 directly contacts AGO2 or acts via RNA remodeling unclear
  13. 2019 High

    AUF1 was shown to participate in DNA double-strand break repair by preventing R-loop accumulation—loss of AUF1 impairs CHK1 activation and homologous recombination, rescuable by RNase H1—revealing a genome-stability function independent of mRNA decay.

    Evidence CRISPR KO, γH2AX foci imaging, RNA:DNA hybrid detection, in vitro DNA resection, RNase H1 rescue

    PMID:30799487

    Open questions at the time
    • Whether AUF1 directly resolves R-loops or prevents their formation unclear
    • Relationship between AUF1 RNA chaperone activity and R-loop suppression not tested
  14. 2022 High

    Identification of FBXW7 as a second E3 ligase for AUF1 during ferroptosis, with AUF1 antagonizing ferroptosis through NRF2 mRNA stabilization and ATF3 mRNA destabilization, connected AUF1 to regulated cell death pathways.

    Evidence Co-IP for FBXW7-AUF1, CHX chase, RIP, AUF1-KO mouse lung ferroptosis in sepsis

    PMID:35391558

    Open questions at the time
    • Whether β-TrCP and FBXW7 target the same or different AUF1 isoforms unclear
    • Degron recognized by FBXW7 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for isoform-specific functional switching (decay vs. stabilization vs. translational activation), how AUF1 transitions between RNA-binding and DNA-binding modes (e.g., TERT promoter, R-loop suppression), and the tissue-specific contributions of individual isoforms in vivo.
  • No high-resolution structure of AUF1-ARE or AUF1-DNA complex available
  • In vivo isoform-specific knockout models not generated
  • Mechanism of AUF1 RNA chaperone activity vs. decay-promoting activity not structurally resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0140098 catalytic activity, acting on RNA 5 GO:0003677 DNA binding 3 GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
BTRCEIF4G1ELAVL1FBXW7HSPA1AHSPB1PABPC1PRMT1
Complex memberships
ASTRC (ARE/signal transduction-regulated complex)NuRD complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 AUF1/hnRNP-D was identified as an integral component of the alpha-globin mRNA stability complex (alpha-complex), interacting with poly(C)-binding proteins alphaCP1 and alphaCP2 via yeast two-hybrid screen; interaction with alphaCP1 was more efficient than with alphaCP2 both in vitro and in vivo, indicating AUF1 can function in both mRNA stabilization and decay. Yeast two-hybrid screen, in vitro binding assays, in vivo co-immunoprecipitation Molecular and cellular biology High 9234743
1997 AUF1-containing ARE-binding complexes in monocytes are regulated by cell adhesion; these complexes are depleted upon monocyte adherence and reformed upon deadhesion, and complex formation and mRNA destabilization are phosphorylation-dependent events sensitive to tyrosine kinase and p38 MAP kinase inhibitors. Gel mobility shift assays, antibody supershift, pharmacological inhibitors Molecular and cellular biology Medium 9199324
1997 AUF1 requires both RNA recognition motifs (RRMs) plus an N-terminal alanine-rich region and a C-terminal glutamine-rich region for highest-affinity ARE binding; the N-terminus is required for dimerization and AUF1 binds AREs as a hexameric protein. Deletion mutagenesis, RNA-binding affinity assays The Journal of biological chemistry High 9346902
1999 AUF1 assembles on U-rich RNA targets by sequential dimer association to form tetramers; sequences C-terminal to the RRMs contribute to tetramer-ARE complex formation but are not required for RNA binding. AUF1-ARE interactions are highly dynamic in solution. Gel mobility shift assay, chemical cross-linking, fluorescence anisotropy, deletion mutant analysis The Journal of biological chemistry High 10559216
1999 AUF1 regulates its own mRNA expression through binding to AU-rich sequences in alternatively spliced 3'-UTR variants; inclusion of a spliceable intron downstream of the stop codon triggers nonsense-mediated mRNA decay (NMD) of AUF1 mRNA variants. Luciferase-AUF1 3'-UTR chimeric transcript assays, deletion analysis Molecular and cellular biology Medium 10330146
1999 Accelerated ARE-dependent decay of GM-CSF mRNA by neonatal mononuclear cell protein is significantly attenuated by immunodepletion of AUF1, demonstrating that AUF1 is directly responsible for developmentally regulated ARE-mediated mRNA turnover. Cell-free mRNA decay assay, AUF1 immunodepletion The Journal of biological chemistry High 10567360
2000 Mg2+-induced conformational changes in the TNFα ARE inhibit AUF1 binding and oligomerization; AUF1 association with the ARE induces formation of a condensed RNA structure distinct from the Mg2+-stabilized fold, suggesting AUF1 remodels local RNA structure as a prerequisite for recruiting additional trans-acting factors. Fluorescence anisotropy, hydrodynamic analysis, resonance energy transfer The Journal of biological chemistry High 11124962 11514570
2002 The p37 and p40 AUF1 isoforms are strongly ubiquitinated in vitro while the p42 and p45 isoforms are not; the exon 7 sequence present in p42/p45 blocks ubiquitination, and deletion of exon 7 from larger isoforms permits ubiquitination and rapid proteasomal turnover. In vitro ubiquitination assay, overexpression of ubiquitin cycle enzymes, proteasome inhibitor studies Nucleic acids research High 12136087
2002 Lactate dehydrogenase (LDH-M) is an ARE-binding protein that directly interacts with AUF1 and hsp-70 on polysomes; LDH polysomal localization is RNA-binding dependent, placing it within the AUF1 mRNA-destabilizing complex. Protein purification, microsequencing, polysome gradient analysis, in vitro co-IP with purified proteins The Journal of biological chemistry High 12107167
2002 AUF1 binds bcl-2 ARE in vitro through its two RRMs (residues 1-257 conserved in all isoforms) as demonstrated by yeast RNA three-hybrid, and increases following UVC-induced apoptosis in a partially caspase-dependent manner. In vitro binding, yeast RNA three-hybrid, UV irradiation, caspase inhibitor treatment The Journal of biological chemistry Medium 11856759
2003 All four AUF1 isoforms undergo rapid, transcription-independent, carrier-mediated, energy-requiring nucleocytoplasmic shuttling; nuclear import signal maps to the C-terminal domain of the two smaller isoforms (p37/p40), while nuclear export is facilitated by exon 7 sequences in the two larger isoforms (p42/p45). A subset of AUF1 isoforms interact directly in vitro and in vivo in the absence of RNA. Heterokaryon shuttling assay, GFP fusion reporter, mutagenesis, in vitro protein interaction with purified recombinant proteins The Journal of biological chemistry High 12668672
2003 p37 AUF1 isoform (and to a lesser extent p40) possesses ARE-mRNA-destabilizing activity when overexpressed; overexpressed p37 AUF1 eliminated the translation-dependent step normally required for ARE-mRNA decay, and p37/p40 are limiting factors facilitating rapid decay of AU-rich mRNAs. Overexpression of individual isoforms, mRNA decay assays, reporter mRNA analysis Molecular and cellular biology High 12944492
2003 AUF1 interacts with ubiquitin-conjugating enzyme E2I, NSEP-1, NSAP-1, and IMP-2 in an isoform-selective manner; NSEP-1 shows endoribonuclease activity in vitro and can bind ARE simultaneously with AUF1. Yeast two-hybrid, in vitro binding confirmation, gel-shift assays with purified proteins Biological chemistry Medium 12674497
2003 p40AUF1 recovered from polysomes in untreated THP-1 cells is phosphorylated on Ser83 and Ser87; TPA treatment causes loss of these phosphorylations coincident with reduced ARE-binding activity and stabilization of IL-1β and TNFα mRNAs. Polysome fractionation, phosphopeptide mapping, phorbol ester treatment The Journal of biological chemistry High 12819195
2004 HuR and AUF1 bind target mRNAs (p21, cyclin D1) on both distinct nonoverlapping sites and common sites in a competitive fashion; in the nucleus they coexist in stable RNP complexes, while in the cytoplasm they bind individually—HuR colocalizing with the translational apparatus and AUF1 with the exosome. Co-immunoprecipitation, subcellular fractionation, RNA-binding competition assays The EMBO journal High 15257295
2004 Selective siRNA knockdown of p40/p45 AUF1 isoforms strongly stabilizes ARE-mRNA reporter (GFP-ARE) and induces GM-CSF production, while knockdown of all isoforms has no effect; this demonstrates that relative isoform levels rather than total AUF1 determine net mRNA stability. siRNA knockdown of specific isoforms, GFP-ARE fluorescence reporter, GM-CSF ELISA Nucleic acids research High 14976220
2000 SAF-B (scaffold attachment factor B), a nuclear matrix-associated protein, interacts specifically with the p45/p42 AUF1 isoforms via their C-terminal exon 7-encoded sequence; p45/p42 and SAF-B colocalize as nuclear speckles, and p45/p42 act as negative regulators of gene expression when complexed with SAF-B. Yeast two-hybrid, co-localization by immunofluorescence, nuclear retention mapping, gene expression reporter assay Archives of biochemistry and biophysics Medium 10933876
2006 AUF1 directly binds eIF4G at a C-terminal site and poly(A)-binding protein (PABP) independently of eIF4G; AUF1-PABP interaction is opposed by AUF1 binding to ARE or Hsp70, suggesting that ARE-mRNA decay involves translation-dependent displacement of AUF1-PABP complexes with unmasking of the poly(A) tail. In vitro binding with purified recombinant proteins, co-immunoprecipitation, synthetic ARE RNA oligonucleotide RNA High 16556936
2006 AUF1 was found to interact with NPM-ALK oncogenic tyrosine kinase by co-immunoprecipitation; AUF1 is phosphorylated by ALK in vitro and hyperphosphorylated in NPM-ALK-expressing cells, which correlates with increased stability of AUF1 target mRNAs encoding key proliferation regulators. Co-immunoprecipitation, in vitro kinase assay, mRNA stability analysis Blood Medium 16835382
2006 AUF1 mediates degradation of DNMT1 mRNA by binding to an AU-rich conserved element in the DNMT1 3'-UTR and targeting it for exosome-mediated destabilization; AUF1 protein levels are regulated by the proteasome in a cell cycle-dependent manner, resulting in cell cycle-specific destabilization of DNMT1 mRNA. RNA-protein binding assay, AUF1 knockdown/siRNA, mRNA stability assay, cell cycle analysis Molecular and cellular biology High 17030625
2006 AUF1 knockout mice develop severe endotoxic shock upon endotoxin challenge due to failure to degrade TNFα and IL-1β mRNAs in macrophages; neutralizing antibodies to both cytokines protect knockout mice, establishing AUF1 as a critical attenuator of inflammatory cytokine mRNA decay. AUF1 knockout mouse model, endotoxin challenge, mRNA half-life assay in macrophages, cytokine neutralization Genes & development High 17085481
2007 AUF1 and TIAR compete for binding to MYC mRNA ARE; AUF1 abundance promotes MYC translation while TIAR suppresses it, both acting via the ARE without affecting mRNA abundance. Genetic experiments confirmed AUF1 and TIAR control proliferation through a MYC-dependent pathway. RNP immunoprecipitation, overexpression/knockdown, polysome profiling, genetic epistasis Nature structural & molecular biology High 17486099
2008 Chaperone Hsp27 is a novel subunit of the AUF1-containing ARE/signal transduction-regulated complex (ASTRC) and is itself an ARE-binding protein essential for rapid ARE-mRNA (TNFα) degradation; activation-induced subunit rearrangements within ASTRC were demonstrated. Co-immunoprecipitation, RNA-binding assays, siRNA knockdown, mRNA decay assays Molecular and cellular biology High 18573886
2008 AUF1 HNRNPD-deficient mice develop chronic pruritic inflammatory dermatitis with elevated IgE, Th2 skewing, and increased IL-2, TNFα, and IL-1β production from T cells and macrophages, establishing AUF1's role in maintaining immune homeostasis through mRNA stability control. AUF1 knockout mouse model, histology, cytokine measurement, contact hypersensitivity assay The Journal of investigative dermatology High 18830269
2008 AUF1 binds the 3'-UTR of SERCA2a mRNA; PMA-induced AUF1 binding to this UTR is associated with increased threonine phosphorylation of AUF1 and is predominantly found in the nuclear fraction, correlating with SERCA2a mRNA destabilization in cardiomyocytes. UV cross-linking, RNA pull-down, Western blot fractionation, RSV reporter system American journal of physiology. Heart and circulatory physiology Medium 16113063
2008 AUF1 interacts with members of the NuRD chromatin remodeling complex—specifically HDAC1 and MTA2—and simultaneously binds AT-rich DNA elements; gene regulatory function is modulated by histone acetylation level, and AUF1-deficient animals show altered complex composition. Co-immunoprecipitation, immunofluorescence co-localization, DNA binding assays, AUF1 knockout comparison Cerebral cortex Medium 18413351
2010 Nucleolin binds the 5' end of the bcl-2 ARE and protects transcripts from exosomal decay; immunodepletion of AUF1 from cell extracts reduces bcl-2 ARE transcript decay rate, indicating AUF1 recruits the exosome while nucleolin opposes this, with competing roles in bcl-2 mRNA stability. RNase footprinting, RNA decay assay, immunodepletion, AUF1/nucleolin pull-down in cell extracts The Journal of biological chemistry High 20571027
2010 HuR destabilizes p16(INK4) mRNA using AUF1 as a cofactor; HuR knockdown reduces AUF1 association with p16 3'-UTR and vice versa; both proteins are required for RISC (Ago2) recruitment to the p16 3'-UTR, and p16 mRNA decay depends on a stem-loop structure in the 3'-UTR. siRNA knockdown, RIP, EGFP-p16 chimeric reporter with stem-loop mutations Molecular and cellular biology High 20498276
2010 The p40 AUF1 isoform selectively plays a critical positive role in LPS-mediated IL-10 mRNA induction in monocytes; AUF1 binds the IL-10 3'-UTR ARE and only p40 (not p37) restores LPS-mediated IL10 mRNA and protein induction upon AUF1 siRNA complementation. siRNA knockdown, isoform-specific re-expression (RNAi-refractory plasmids), luciferase ARE reporter, mRNA stability assay Journal of interferon & cytokine research High 18844578
2011 Phosphomimetic Hsp27 mutants promote proteasome-dependent proteolysis of AUF1 and stabilize ARE-mRNAs; the p38 MAPK–MK2–Hsp27 signaling axis targets AUF1 for destruction by proteasomes. Hsp27 phosphomimetic mutant overexpression, proteasome inhibition, mRNA stability assay, AUF1 protein level analysis Molecular and cellular biology High 21245386
2012 AUF1 binds and strongly activates the transcription promoter for telomerase catalytic subunit Tert; AUF1-deficient mice undergo telomere erosion, DNA damage, cellular senescence, and premature aging that is rescued by resupplying AUF1. AUF1 also destabilizes cell-cycle checkpoint mRNAs to prevent senescence. AUF1 knockout mouse, promoter binding assays, telomere length analysis, AUF1 rescue by re-expression Molecular cell High 22633954
2012 AUF1 associates with DICER1 mRNA within coding region and 3'-UTR and lowers DICER1 mRNA stability; silencing AUF1 lengthens DICER1 mRNA half-life and increases Dicer expression and mature miRNA levels, while AUF1 overexpression reduces Dicer and miRNAs. RIP, mRNA half-life assay, AUF1 knockdown/overexpression, pre-miRNA vs. mature miRNA quantification Nucleic acids research High 23066106
2012 AUF1 p40 isoform specifically binds EBER1 noncoding RNA in EBV-infected cells; EBER1 competes with ARE-containing mRNA for AUF1 p40 binding as shown by EMSA competition assays. MS2-mediated RNA selection with SILAC mass spectrometry, UV crosslinking, EMSA competition assay RNA High 23012480
2013 β-TrCP (F-box substrate recognition subunit of SCF E3 ligase) promotes ubiquitination and degradation of AUF1; Hsp27 phosphomimetic mutants are required together with AUF1 phosphorylation for enhanced β-TrCP-mediated AUF1 degradation, stabilizing cytokine ARE-mRNAs. β-TrCP siRNA knockdown/overexpression, ubiquitination assay, mRNA stability reporter Molecular and cellular biology High 23530064
2013 All four AUF1 isoforms bind directly to stem-loop IV of the poliovirus 5' NCR; AUF1 inhibits viral translation and titers (antiviral role); viral proteinase 3CD cleavage of AUF1 inhibits this interaction, and AUF1 relocalization to the cytoplasm during infection is driven by viral protein 2A. In vitro binding assays, viral titer analysis, AUF1 knockdown, immunofluorescence colocalization Journal of virology High 23903828
2013 CVB3 infection causes cytoplasmic redistribution of AUF1 (driven by viral protease 2A) and AUF1 cleavage by viral protease 3C; AUF1 knockdown facilitates viral RNA/protein production; AUF1 physically interacts with the 3'-UTR of CVB3 genome by co-immunoprecipitation, suggesting antiviral RNA targeting. Subcellular fractionation, in vitro cleavage assay, AUF1 knockdown, co-immunoprecipitation FASEB journal High 23572232
2014 PAR-CLIP analysis reveals AUF1 primarily recognizes U-/GU-rich sequences in mRNAs and noncoding RNAs; AUF1 lowers steady-state levels of numerous targets including lncRNA NEAT1 (affecting nuclear paraspeckle organization), promotes translation of other targets without changing abundance, and stabilizes mRNAs encoding DNA-maintenance proteins to preserve genomic integrity. PAR-CLIP, ribosome profiling, NEAT1/paraspeckle imaging, AUF1 knockdown Nature communications High 25366541
2014 AUF1 p45 exhibits RNA chaperone activity that enables structural rearrangement and cyclization of West Nile virus RNA genome; this chaperone activity supports viral replicase initiation and is a key determinant of WNV replication. In vitro RNA cyclization assay, cell-based WNV replication assay, AUF1 isoform comparison Journal of virology High 25078689
2014 AUF1 p45 interacts with TTP family tandem zinc finger domains; AUF1 p45 (but not p37) increases TTP binding affinity for ARE-containing RNA ~5-fold as demonstrated by FRET assays with purified recombinant proteins and synthetic RNA, suggesting isoform-specific AUF1 co-activation of TTP-family mRNA decay. Co-immunoprecipitation in cell extracts, RNA gel shift, FRET with purified proteins The Journal of biological chemistry High 22203679
2014 AUF1 binds specifically to RNA containing oxidized guanine (8-oxo-7,8-dihydroguanine); AUF1-deficient HeLa and Nalm-6 cells exhibit higher levels of oxidized mRNA and growth retardation, implicating AUF1 in elimination of oxidatively damaged RNA. AUF1 knockout by gene targeting, oxidized mRNA quantification, mRNA stability analysis, in vitro binding to 8-oxoG RNA Free radical biology & medicine High 25486179
2014 AUF1 binds Cry1 3'-UTR and promotes its translation by interacting with eIF3b and directly associating with ribosomal proteins S3 and S14, facilitating 40S ribosomal subunit recruitment and rhythmic CRY1 protein synthesis. RIP, co-immunoprecipitation with ribosomal proteins, translation assay with 3'-UTR reporter, circadian time-course analysis Nucleic acids research Medium 24423872
2016 The arginine methyltransferase PRMT1 methylates the C-terminus of AUF1 p45; methylated AUF1 p45 shows increased affinity for WNV RNA termini, enhanced RNA chaperone activity, and more efficient stimulation of viral RNA synthesis; AUF1 p45 also has an RNA annealing activity unaffected by methylation. PRMT1 knockdown, mass spectrometry of methylation sites, RNA binding affinity measurements, RNA chaperone and annealing assays in vitro RNA High 27520967
2018 AUF1 p45 supports replication of dengue virus and Zika virus (in addition to WNV) as a general flavivirus host factor; it destabilizes 3'-terminal stem-loop (3'SL) and 5'-SLB to expose UAR cyclization elements while not modulating the SLA promoter structure, enabling viral RNA-dependent RNA polymerase initiation. RNA structure analysis, in vitro RNA cyclization assay, cell-based flavivirus replication assays Journal of virology High 29263261
2019 HNRNPD/AUF1 binds chromatin and relocalizes to γH2Ax foci upon DNA damage; HNRNPD depletion impairs CHK1 S345 phosphorylation, DNA end resection, and homologous recombination; depletion increases RNA:DNA hybrids upon damage, and RNase H1 expression or RNA pol II inhibition rescues defective RPA32 S4/8 phosphorylation in HNRNPD knockout cells. CRISPR/Cas9 knockout, synthetic DNA bait pulldown + LC-MS, in vitro DNA resection assay, γH2Ax foci imaging, RNA:DNA hybrid detection Nucleic acids research High 30799487
2019 AUF1 orchestrates staged muscle development by targeted decay of fate-determining checkpoint mRNAs: AUF1 degrades Twist1 mRNA to promote myoblast development, CyclinD1 mRNA to block proliferation and initiate differentiation, and RGS5 mRNA to activate Sonic Hedgehog pathway-mediated myotube formation. AUF1 transcription in satellite cells is activated by CTCF. AUF1 depletion mouse model, satellite cell explants, mRNA decay assays for specific targets, myogenesis stage phenotyping Proceedings of the National Academy of Sciences of the United States of America High 31113881
2021 CircPCNX (hsa_circ_0032434) interacts with AUF1 and specifically prevents AUF1 binding to p21 (CDKN1A) mRNA, thereby promoting p21 mRNA stability and p21 protein production, suppressing cell proliferation; elimination of the AUF1-binding region of circPCNX abolishes this effect. RIP, circPCNX overexpression/silencing, AUF1-binding region deletion in circPCNX, cell proliferation assays Nucleic acids research High 33444453
2022 FBXW7 E3 ubiquitin ligase mediates ubiquitination and proteasomal degradation of AUF1 during ferroptosis; AUF1 antagonizes ferroptosis by up-regulating NRF2 mRNA and down-regulating ATF3 mRNA stability via direct binding, and AUF1 knockout in mice enhances lung ferroptosis in sepsis. Cycloheximide chase, co-IP for FBXW7-AUF1, RIP, RNA pull-down, mRNA stability assays, AUF1 knockout mouse model Cellular and molecular life sciences High 35391558
2017 AUF1 facilitates miRNA loading to Argonaute 2 (AGO2); depletion of AUF1 abolishes global miRNA–AGO2 interactions; single-molecule analysis shows AUF1 slows AGO2-let-7b-mRNA complex assembly, yet AUF1 overexpression promotes decay of mRNAs recognized by both miRNA and AUF1, indicating AUF1 acts at multiple steps in miRNA-mediated mRNA decay. AGO2 RIP upon AUF1 depletion, single-molecule FRET analysis, AUF1 overexpression/knockdown mRNA abundance Nucleic acids research High 28334781
2006 Two AUF1 3'-UTR mRNA variants are NMD substrates; Upf1 and Upf2 associate with NMD-sensitive AUF1 mRNA 3'-UTR variants by RNP immunoprecipitation; disruption of Upf1/Upf2 by RNAi stabilizes these transcripts, linking NMD and ARE-mediated mRNA decay pathways. Upf1/Upf2 siRNA knockdown, dominant-negative Upf1, RNP-IP, mRNA variant quantification during embryogenesis Molecular and cellular biology High 17000771

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs. The EMBO journal 412 15257295
2006 Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes & development 177 17085481
2010 The role of AUF1 in regulated mRNA decay. Wiley interdisciplinary reviews. RNA 160 21956942
2004 Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by RNA interference. Nucleic acids research 159 14976220
2007 Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nature structural & molecular biology 155 17486099
2020 Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Molecular cancer 149 32020881
2014 PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nature communications 141 25366541
1997 Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the alpha-globin mRNA stability complex. Molecular and cellular biology 139 9234743
1997 Adhesion-dependent regulation of an A+U-rich element-binding activity associated with AUF1. Molecular and cellular biology 135 9199324
2002 A new player in oncogenesis: AUF1/hnRNPD overexpression leads to tumorigenesis in transgenic mice. Cancer research 129 11888925
2003 Selective degradation of AU-rich mRNAs promoted by the p37 AUF1 protein isoform. Molecular and cellular biology 119 12944492
2012 mRNA decay factor AUF1 maintains normal aging, telomere maintenance, and suppression of senescence by activation of telomerase transcription. Molecular cell 117 22633954
2010 HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology 114 20102719
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2010 HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay. Molecular and cellular biology 101 20498276
2003 Nuclear import and export functions in the different isoforms of the AUF1/heterogeneous nuclear ribonucleoprotein protein family. The Journal of biological chemistry 100 12668672
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2010 Mechanism of regulation of bcl-2 mRNA by nucleolin and A+U-rich element-binding factor 1 (AUF1). The Journal of biological chemistry 90 20571027
2022 AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3. Cellular and molecular life sciences : CMLS 88 35391558
2002 AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis. The Journal of biological chemistry 88 11856759
1999 Assembly of AUF1 oligomers on U-rich RNA targets by sequential dimer association. The Journal of biological chemistry 86 10559216
2016 AUF1 regulation of coding and noncoding RNA. Wiley interdisciplinary reviews. RNA 84 27620010
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2014 Physiological networks and disease functions of RNA-binding protein AUF1. Wiley interdisciplinary reviews. RNA 80 24687816
2014 The cytokine IL-6 reactivates breast stromal fibroblasts through transcription factor STAT3-dependent up-regulation of the RNA-binding protein AUF1. The Journal of biological chemistry 76 25231991
2002 Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1. The Journal of biological chemistry 74 12107167
2012 AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein-Barr virus. RNA (New York, N.Y.) 71 23012480
2021 AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production. Nucleic acids research 70 33444453
2008 Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. The Journal of investigative dermatology 69 18830269
2004 Structural and functional dissection of a conserved destabilizing element of cyclo-oxygenase-2 mRNA: evidence against the involvement of AUF-1 [AU-rich element/poly(U)-binding/degradation factor-1], AUF-2, tristetraprolin, HuR (Hu antigen R) or FBP1 (far-upstream-sequence-element-binding protein 1). The Biochemical journal 68 14594446
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2000 A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D. Archives of biochemistry and biophysics 65 10933876
2005 Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization. The Journal of biological chemistry 64 16109718
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2012 RNA-binding protein AUF1 represses Dicer expression. Nucleic acids research 60 23066106
2000 Folding of A+U-rich RNA elements modulates AUF1 binding. Potential roles in regulation of mRNA turnover. The Journal of biological chemistry 60 11124962
2019 LINC01354 interacting with hnRNP-D contributes to the proliferation and metastasis in colorectal cancer through activating Wnt/β-catenin signaling pathway. Journal of experimental & clinical cancer research : CR 58 30987669
2010 Polyamines regulate the stability of JunD mRNA by modulating the competitive binding of its 3' untranslated region to HuR and AUF1. Molecular and cellular biology 58 20805360
2013 Cellular mRNA decay protein AUF1 negatively regulates enterovirus and human rhinovirus infections. Journal of virology 57 23903828
1999 Developmental regulation of RNA transcript destabilization by A + U-rich elements is AUF1-dependent. The Journal of biological chemistry 56 10567360
2012 Sequence requirements for RNA binding by HuR and AUF1. Journal of biochemistry 55 22368252
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2011 Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation. Molecular and cellular biology 52 21245386
2019 Depletion of the RNA binding protein HNRNPD impairs homologous recombination by inhibiting DNA-end resection and inducing R-loop accumulation. Nucleic acids research 51 30799487
1999 Regulation of AUF1 expression via conserved alternatively spliced elements in the 3' untranslated region. Molecular and cellular biology 51 10330146
2019 Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis. Medical science monitor : international medical journal of experimental and clinical research 50 30681073
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2011 p16( INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1. PloS one 49 21799732
2015 Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis. Molecular human reproduction 48 26433194
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2001 Structural remodeling of an A + U-rich RNA element by cation or AUF1 binding. The Journal of biological chemistry 46 11514570
2014 AUF1 p45 promotes West Nile virus replication by an RNA chaperone activity that supports cyclization of the viral genome. Journal of virology 45 25078689
2008 AUF1 isoform-specific regulation of anti-inflammatory IL10 expression in monocytes. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 45 18844578
2006 A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK. Blood 45 16835382
2013 Cytoplasmic redistribution and cleavage of AUF1 during coxsackievirus infection enhance the stability of its viral genome. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 42 23572232
2006 Differential stability of thymidylate synthase 3'-untranslated region polymorphic variants regulated by AUF1. The Journal of biological chemistry 42 16787927
2017 AUF1 facilitates microRNA-mediated gene silencing. Nucleic acids research 41 28334781
2011 MKP-1 regulates cytokine mRNA stability through selectively modulation subcellular translocation of AUF1. Cytokine 41 21733716
2010 AUF1 is involved in splenic follicular B cell maintenance. BMC immunology 41 20064252
2023 N6 -methyladenosine-modified circSTX6 promotes hepatocellular carcinoma progression by regulating the HNRNPD/ATF3 axis and encoding a 144 amino acid polypeptide. Clinical and translational medicine 40 37877357
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2011 Direct binding of specific AUF1 isoforms to tandem zinc finger domains of tristetraprolin (TTP) family proteins. The Journal of biological chemistry 32 22203679
2016 Upregulation of AUF1 is involved in the proliferation of esophageal squamous cell carcinoma through GCH1. International journal of oncology 30 27826622
2009 AUF1 and Hu proteins in the developing rat brain: implication in the proliferation and differentiation of neural progenitors. Journal of neuroscience research 30 19115409
2014 Reduction of AUF1-mediated follistatin mRNA decay during glucose starvation protects cells from apoptosis. Nucleic acids research 29 25159612
2021 HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis. Cell death & disease 28 33542193
2018 The Host Factor AUF1 p45 Supports Flavivirus Propagation by Triggering the RNA Switch Required for Viral Genome Cyclization. Journal of virology 28 29263261
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2005 Phosphorylation and binding of AUF1 to the 3'-untranslated region of cardiomyocyte SERCA2a mRNA. American journal of physiology. Heart and circulatory physiology 28 16113063
2023 AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis. Cellular and molecular life sciences : CMLS 27 37589744
2021 Tocilizumab suppresses the pro-carcinogenic effects of breast cancer-associated fibroblasts through inhibition of the STAT3/AUF1 pathway. Carcinogenesis 27 34718441
2006 Upf1/Upf2 regulation of 3' untranslated region splice variants of AUF1 links nonsense-mediated and A+U-rich element-mediated mRNA decay. Molecular and cellular biology 27 17000771
2019 Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs. Proceedings of the National Academy of Sciences of the United States of America 26 31113881
2011 Association of the von Hippel-Lindau protein with AUF1 and posttranscriptional regulation of VEGFA mRNA. Molecular cancer research : MCR 26 22086907
2010 AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay. Nucleic acids research 26 20716519
2016 p16INK4A induces senescence and inhibits EMT through microRNA-141/microRNA-146b-5p-dependent repression of AUF1. Molecular carcinogenesis 25 27596953
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2009 The role of AUF1 in thyroid carcinoma progression. Endocrine-related cancer 24 19574297
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2018 RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma. Oncotarget 21 29599909
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2008 Members of the NuRD chromatin remodeling complex interact with AUF1 in developing cortical neurons. Cerebral cortex (New York, N.Y. : 1991) 21 18413351
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2006 AUF-1 mediates inhibition by nitric oxide of lipopolysaccharide-induced matrix metalloproteinase-9 expression in cultured astrocytes. Journal of neuroscience research 20 16683234
2004 Stability of A+U-rich element binding factor 1 (AUF1)-binding messenger ribonucleic acid correlates with the subcellular relocalization of AUF1 in the rat uterus upon estrogen treatment. Molecular endocrinology (Baltimore, Md.) 20 15192077