Affinage

Showing HNRNPD — AUF1 is a alias.

HNRNPD

Heterogeneous nuclear ribonucleoprotein D0 · UniProt Q14103

Length
355 aa
Mass
38.4 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPD/AUF1 is a family of four alternatively spliced RNA-binding protein isoforms (p37, p40, p42, p45) generated from a single gene that controls post-transcriptional gene expression chiefly by recognizing U-/AU-rich elements (AREs) in mRNA 3'-UTRs and directing target mRNA decay (PMID:8246982, PMID:9521873, PMID:12944492, PMID:25366541). High-affinity ARE recognition is achieved through two RNA recognition motifs assisted by N- and C-terminal accessory regions; AUF1 binds as a dimer that cross-links into tetramers/hexamers and remodels the bound RNA into a condensed structure, with oligomerization being essential for high-affinity binding (PMID:9346902, PMID:10559216, PMID:11514570, PMID:20926381). On target mRNAs AUF1 nucleates a decay-competent ribonucleoprotein complex, interacting with translation initiation factor eIF4G and poly(A)-binding protein independently of ARE binding and partitioning with the exosome in the cytoplasm, thereby coupling translation status to deadenylation and degradation (PMID:15257295, PMID:16556936). AUF1 activity is governed by isoform-specific, energy-dependent nucleocytoplasmic shuttling — nuclear import via a C-terminal signal in p37/p40 and exon-7-mediated export in p42/p45, with SAF-B retaining p42/p45 in the nucleus and 14-3-3σ driving cytoplasmic accumulation of p37 — and by proteolytic control, since p37/p40 are selectively ubiquitinated and degraded while exon 7 blocks this fate (PMID:10933876, PMID:12136087, PMID:12668672, PMID:16902409). Multiple signaling inputs (p38-MK2-Hsp27, β-TrCP, FBXW7) tune AUF1 abundance through the proteasome to set ARE-mRNA stability (PMID:21245386, PMID:23530064, PMID:35391558). Physiologically, AUF1 is a critical attenuator of inflammation, since knockout mice fail to degrade TNFα and IL-1β mRNAs and develop endotoxic shock (PMID:17085481), and it governs muscle satellite cell fate and regeneration by stage-specific decay of checkpoint mRNAs such as MMP9, Twist1, and CyclinD1 (PMID:27452471, PMID:31113881). Beyond decay, AUF1 promotes translation of select mRNAs, loads let-7 microRNA onto AGO2, preserves genomic integrity by facilitating DNA end resection and suppressing R-loops at double-strand breaks, and acts as an RNA chaperone that drives flavivirus genome cyclization (PMID:25366541, PMID:26253535, PMID:30799487, PMID:29263261).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1993 High

    Established AUF1 as the RNA-binding component of an mRNA degradation activity, defining its founding biochemical identity.

    Evidence Biochemical purification from K562 postribosomal supernatant, UV crosslinking, and cDNA cloning revealing two RRMs

    PMID:8246982

    Open questions at the time
    • Did not resolve which specific mRNA sequences are targeted
    • Did not establish in vivo decay specificity
  2. 1998 High

    Showed the four isoforms arise from alternative splicing of one gene with distinct RNA-binding properties, framing isoform-specific function.

    Evidence Genomic cloning, FISH, RT-PCR and immunoblot

    PMID:9521873

    Open questions at the time
    • Did not assign distinct cellular roles to each isoform
    • Did not define structural basis of differential affinity
  3. 2001 High

    Defined the structural and biophysical mechanism of ARE recognition, showing oligomerization and RNA remodeling underlie high-affinity binding.

    Evidence Deletion mutagenesis, cross-linking, fluorescence anisotropy, FRET, and NMR structure of RBD2

    PMID:10559216 PMID:11514570 PMID:11531333 PMID:9346902

    Open questions at the time
    • No full-length multi-domain structure on RNA
    • Stoichiometry on physiological transcripts not resolved
  4. 2003 High

    Linked isoform-specific subcellular trafficking and proteasomal turnover to AUF1 regulation, explaining how its activity is spatially and quantitatively controlled.

    Evidence Heterokaryon shuttling assays, GFP reporters, mutagenesis, yeast two-hybrid (SAF-B), and in vitro ubiquitination reconstitution

    PMID:10933876 PMID:12136087 PMID:12668672

    Open questions at the time
    • Did not identify the import/export receptors
    • Did not identify the responsible E3 ligase at this stage
  5. 2006 High

    Connected AUF1 to the translation machinery and demonstrated its in vivo role as an inflammation attenuator, establishing physiological significance.

    Evidence In vitro reconstitution with eIF4G/PABP, Co-IP, AUF1 knockout mouse endotoxin challenge with neutralizing-antibody rescue, and ARE-mRNA decay assays

    PMID:13 PMID:16556936 PMID:16902409 PMID:16954375 PMID:17085481

    Open questions at the time
    • Mechanism coupling translation displacement to decay not fully resolved
    • Exosome recruitment biochemistry not reconstituted
  6. 2010 High

    Showed AUF1 cooperates with other ARE-binding proteins and the RISC machinery to control proliferation and senescence checkpoints.

    Evidence Double-knockdown epistasis, RIP, reporter assays with HuR/TIAR and Ago2 co-IP across MYC, p16, p21 targets

    PMID:12944492 PMID:17486099 PMID:20498276

    Open questions at the time
    • Rules governing competitive vs cooperative co-binding not generalized
    • Direct AUF1-Ago2 contacts not mapped
  7. 2014 High

    Transcriptome-wide mapping revealed AUF1 acts beyond decay — promoting translation and stabilizing DNA-maintenance mRNAs to preserve genome integrity and prevent senescence.

    Evidence PAR-CLIP, ribosome profiling, RNA-seq with knockdown senescence/DNA-damage phenotyping; let-7-AGO2 loading by single-molecule analysis

    PMID:25366541 PMID:26253535

    Open questions at the time
    • Determinants distinguishing stabilized vs destabilized targets unclear
    • Mechanism of translational enhancement not defined
  8. 2018 High

    Identified AUF1 p45 as an RNA chaperone that drives flavivirus genome cyclization, extending its function to viral RNA structural remodeling.

    Evidence In vitro SHAPE/chemical probing of viral RNA and isoform-specific cell-based replication assays for West Nile, dengue and Zika viruses

    PMID:25078689 PMID:29263261

    Open questions at the time
    • Structural basis of isoform-specific chaperone activity unresolved
    • Whether host RNAs are similarly remodeled not addressed
  9. 2019 High

    Placed AUF1 directly in the DNA damage response, demonstrating it promotes end resection and suppresses R-loops at break sites.

    Evidence siRNA/CRISPR KO, in vitro resection assay, γH2Ax foci colocalization, RNA:DNA hybrid detection with RNase H1 rescue, SAF-A Co-IP

    PMID:30799487

    Open questions at the time
    • How RNA binding mechanistically enables resection unclear
    • Direct substrate RNAs at damage sites not identified
  10. 2022 Medium

    Identified FBXW7 as an E3 ligase degrading AUF1 during ferroptosis and connected AUF1 to NRF2/ATF3 redox control.

    Evidence Co-IP, cycloheximide chase, RIP, RNA pulldown and mRNA stability assays

    PMID:35391558

    Open questions at the time
    • Single lab; degron and ubiquitination sites not mapped
    • Direct vs indirect regulation of NRF2/ATF3 not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AUF1 isoform composition, post-translational modification, and partner availability are integrated to switch a given transcript between decay, stabilization, and translational enhancement remains unresolved.
  • No predictive rule for decay vs stabilization outcome
  • No full-length isoform-RNA structure
  • Mechanistic coupling of nuclear (resection, R-loop) and cytoplasmic (decay, translation) roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0045182 translation regulator activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0003677 DNA binding 2 GO:0044183 protein folding chaperone 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 5 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-73894 DNA Repair 1
Partners
AGO2EIF4G1HUR/ELAVL1PABPC1SAFA/HNRNPUSAFBYBX1YWHAS/SFN

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 AUF1 (p37 and p40 isoforms) was purified from K562 cell postribosomal supernatant as the RNA-binding component of mRNA degradation activity; both polypeptides are phosphorylated, form complexes with other polypeptides, and are found in both nucleus and cytoplasm. cDNA cloning revealed two RNA recognition motifs (RRMs) and domains mediating protein-protein interactions. Biochemical purification, UV crosslinking, immunoprecipitation, cDNA cloning, immunoblot Molecular and cellular biology High 8246982
1997 High-affinity AUF1 binding to AREs requires both RRMs plus an N-terminal alanine-rich region and a C-terminal glutamine-rich region. The N-terminus is required for dimerization, and AUF1 binds an ARE as a hexameric protein, indicating protein-protein interactions are essential for high-affinity ARE binding. In vitro RNA binding assays with AUF1 deletion mutants, gel mobility shift assays The Journal of biological chemistry High 9346902
1998 The four AUF1 isoforms (p37, p40, p42, p45) are generated by alternative pre-mRNA splicing of a single gene at chromosome 4q21.1-q21.2; the different isoforms exhibit different RNA-binding affinities and specificities. Genomic cloning, Southern blotting, FISH, RT-PCR, immunoblot Genomics High 9521873
1999 AUF1 assembles on U-rich ARE RNA by sequential dimer binding: AUF1 dimers cross-link to form tetramers on high-affinity RNA targets. Sequences C-terminal to the RRMs contribute to tetramer-ARE complex formation but are not required for RNA binding. ARE-AUF1 complexes are highly dynamic in solution. Gel mobility shift assay, chemical cross-linking, fluorescence anisotropy with fluorescent RNA substrates, deletion mutant analysis The Journal of biological chemistry High 10559216
1999 AUF1 mRNA contains alternative 3'-UTR splice variants including a conserved 107-nt exon 9; inclusion of a spliceable intron 9 downstream of the stop codon triggers nonsense-mediated mRNA decay, providing a self-regulatory mechanism for AUF1 expression. Intronic AUF1-binding sequences in the unspliceable form also repress expression in cis. Luciferase-AUF1 3'UTR chimeric transcript reporter assays, deletion analysis Molecular and cellular biology Medium 10330146
2000 SAF-B (scaffold attachment factor B), a nuclear matrix-associated protein, interacts specifically with the p42/p45 AUF1 isoforms via their C-terminal exon 7-encoded sequence. This interaction retains p42/p45 in the nucleus (nuclear retention activity mapped to exon 7 region), while p40/p37 undergo continuous nucleocytoplasmic shuttling. p45/p42 isoforms act as negative regulators of gene expression by forming a complex with SAF-B. Yeast two-hybrid screening, in vitro binding confirmation, heterokaryon shuttling assay, RNA Pol II inhibitor treatment, colocalization by immunofluorescence Archives of biochemistry and biophysics High 10933876
2000 AUF1 functions as the DNA-binding component CBF2 at the Epstein-Barr virus C promoter (Cp); AUF1 binds a specific sequence within the EBNA2 enhancer in Cp, and stimulation of the cAMP/PKA signaling pathway increases AUF1/CBF2 binding activity and enhances EBNA2-mediated transcriptional activation. Biochemical purification of CBF2, microsequencing, antibody supershift in EMSA, cAMP/PKA stimulation assays, transfection reporter assays Journal of virology High 10933728
2001 AUF1 binding to ARE RNA induces condensation of the RNA into a compact structure distinct from the folded structure stabilized by multivalent cations (Mg2+). Mg2+-induced folding of the TNFα ARE inhibits AUF1 binding and oligomerization. Fluorescence resonance energy transfer (FRET), gel mobility shift assays, fluorescence anisotropy The Journal of biological chemistry High 11514570
2001 NMR structure of the C-terminal RBD (RBD2) of hnRNP D0/AUF1 reveals a five-stranded antiparallel beta-sheet packed against two alpha-helices; chemical shift perturbation showed that the beta4(-) to beta4 region contacts RNA (and DNA in essentially the same way). Slow conformational exchange in the beta4(-) to beta4 region of free RBD2 is quenched upon complex formation with DNA. NMR structure determination, relaxation/dynamics analysis, chemical shift perturbation mapping Journal of molecular biology High 11531333
2002 The p37 and p40 AUF1 isoforms are selectively ubiquitinated and degraded by the proteasome, whereas p42 and p45 are not. The C-terminal exon 7 sequence (present only in p42/p45) blocks ubiquitination; deletion of exon 7 permits ubiquitination and rapid degradation of normally stable AUF1 proteins. In vitro ubiquitination system, overexpression of ubiquitin-cycle enzymes, proteasome inhibitor assays, deletion mutagenesis Nucleic acids research High 12136087
2003 All four AUF1 isoforms undergo rapid, transcription-independent, carrier-mediated, energy-requiring nucleocytoplasmic shuttling. Nuclear import is mediated by a C-terminal signal found only in the two smaller isoforms (p37, p40); nuclear export is facilitated by exon 7 sequences found only in the two larger isoforms (p42, p45). A subset of AUF1 proteins directly interact in vitro and in vivo in the absence of RNA, forming heterocomplexes that may co-shuttle. Heterokaryon shuttling assay, GFP fusion reporter constructs, mutagenesis mapping, in vitro protein interaction with purified recombinant proteins, leptomycin B treatment The Journal of biological chemistry High 12668672
2003 The p37 AUF1 isoform (and to a lesser extent p40) possesses ARE-mRNA destabilizing activity when overexpressed and is a limiting component for ARE-mRNA decay. p37 AUF1 overexpression restores rapid degradation of ARE-mRNAs in cells where this activity is saturated, and eliminates the translation-dependent step normally required for ARE-mRNA decay. Overexpression of individual AUF1 isoforms, mRNA half-life measurements, reporter mRNA assays Molecular and cellular biology High 12944492
2003 AUF1 interacts with ubiquitin-conjugating enzyme E2I, and the RNA-binding proteins NSEP-1, NSAP-1, and IMP-2 in a yeast two-hybrid screen; all interactions were confirmed in vitro with purified proteins. NSEP-1 showed endoribonuclease activity in vitro. The interacting proteins can simultaneously bind an AU-rich RNA oligonucleotide with AUF1. Yeast two-hybrid, in vitro binding with recombinant proteins, domain mapping, gel-shift assays with recombinant proteins Biological chemistry Medium 12674497
2004 HuR and AUF1 can bind common target mRNAs (p21, cyclin D1) on both distinct nonoverlapping sites and on common sites in a competitive fashion. In the nucleus, both proteins are found together in stable ribonucleoprotein complexes; in the cytoplasm, HuR colocalizes with the translational apparatus and AUF1 colocalizes with the exosome. RNP immunoprecipitation, UV crosslinking, sucrose gradient fractionation, immunofluorescence colocalization The EMBO journal High 15257295
2006 All four AUF1 isoforms bind directly to translation initiation factor eIF4G at its C-terminal site, independently of ARE binding. AUF1 also directly interacts with poly(A)-binding protein (PABP) both independently of and in complex with eIF4G; AUF1-PABP interaction is opposed by AUF1 binding to the ARE or Hsp70. A model is proposed in which translation-dependent displacement of AUF1-PABP complexes from ARE-mRNAs may unmask the poly(A) tail. Purified recombinant proteins with synthetic ARE RNA, in vitro binding assays, co-immunoprecipitation in vivo RNA (New York, N.Y.) High 16556936
2006 AUF1 binds to the AU-rich element in the IL-6 mRNA 3'-UTR in vivo and promotes its degradation; both p37 and p42 isoforms are active. Overexpression of AUF1 destabilizes IL-6 mRNA, and RNAi knockdown stabilizes it. A cooperating 5' stem-loop structure is also required for full instability. Reporter mRNA stability assays (GFP chimeras), siRNA knockdown, scanning mutagenesis, myc-tagged AUF1 co-immunoprecipitation of IL-6 mRNA Molecular and cellular biology High 16954375
2006 14-3-3σ selectively binds to p37 AUF1 (and to a lesser extent p40) at a region overlapping the nuclear localization signal. 14-3-3σ overexpression increases cytoplasmic accumulation of p37 AUF1 and reduces ARE-mRNA half-life; siRNA silencing of AUF1 eliminates this effect, indicating 14-3-3σ promotes ARE-mRNA decay by retaining p37 AUF1 in the cytoplasm. Mass spectrometry identification of AUF1-interacting proteins, co-immunoprecipitation, subcellular fractionation, siRNA knockdown, ARE-mRNA reporter half-life assays The EMBO journal High 16902409
2006 AUF1 is phosphorylated by the oncogenic tyrosine kinase NPM-ALK in vitro, and is hyperphosphorylated in NPM-ALK-expressing cells. AUF1 co-immunoprecipitates with ALK in ALCL cells and NIH3T3 cells expressing NPM-ALK. Hyperphosphorylation of AUF1 correlates with increased stability of AUF1 target mRNAs encoding cell-proliferation regulators. Co-immunoprecipitation, in vitro kinase assay, phosphorylation analysis, mRNA stability assays Blood Medium 16835382
2006 AUF1 destabilizes DNMT1 mRNA by binding to an AU-rich conserved element in DNMT1 3'-UTR and targeting it for exosome-mediated degradation. AUF1 protein levels are regulated by the proteasome in a cell-cycle-dependent manner, creating cell cycle-specific DNMT1 mRNA destabilization. AUF1 knockdown leads to DNMT1 overexpression, increased DNA methyltransferase activity, and genome hypermethylation. RIP, mRNA stability assays, AUF1 siRNA knockdown, DNMT1 reporter assays, methylation analysis Molecular and cellular biology High 17030625
2006 AUF1 knockout mice develop severe endotoxic shock upon bacterial endotoxin challenge due to failure to degrade TNFα and IL-1β mRNAs in macrophages. This demonstrates AUF1 functions as a crucial attenuator of the inflammatory response by promoting rapid decay of selective proinflammatory cytokine mRNAs following endotoxin activation. AUF1 knockout mouse model, endotoxin challenge, mRNA decay assays, neutralizing antibody rescue experiments Genes & development High 17085481
2007 AUF1 and TIAR compete for binding to MYC mRNA ARE; AUF1 promotes MYC translation while TIAR suppresses it. MYC translation and cell proliferation are proportional to AUF1 abundance and inversely proportional to TIAR abundance. Altering one ARE-binding protein's association with MYC mRNA reciprocally affects the other's binding. Genetic experiments show AUF1 and TIAR control proliferation through a MYC-dependent pathway. RIP, polysome analysis, cell proliferation assays, genetic epistasis with siRNA knockdown Nature structural & molecular biology High 17486099
2010 All four AUF1 isoforms exist as dimers in solution. Exon 2-encoded sequences inhibit RNA-binding affinity, while exon 7-encoded sequences enhance RNA-dependent protein oligomerization and can confer cooperative RNA-binding in some contexts. Different AUF1 isoforms remodel bound RNA substrates into divergent structures as a function of protein:RNA stoichiometry. Chemical cross-linking, gel filtration chromatography, EMSA, fluorescence anisotropy, FRET-based RNA structure assays, purified recombinant isoforms The Journal of biological chemistry High 20926381
2010 HuR destabilizes p16(INK4) mRNA using AUF1 as a cofactor; knockdown of either alone increases p16 expression, but concomitant knockdown has much weaker effect. AUF1 and HuR mutually enhance each other's binding to the p16 3'UTR, and both recruit Ago2/RISC to destabilize p16 mRNA. The secondary stem-loop structure in p16 3'UTR is required for this effect. siRNA knockdown (single and double KD), RIP, EGFP-p16 chimeric reporter assays with stem-loop mutations, Ago2 co-IP Molecular and cellular biology High 20498276
2010 The p40 AUF1 isoform selectively promotes LPS-induced IL10 mRNA induction and expression in monocytes; p37 does not rescue AUF1-depleted cells. AUF1 (p40) maintains proper levels of kinase TAK1 by promoting its mRNA translation (not stability), thereby activating IKKβ and NF-κB signaling to permit IL10 induction. siRNA knockdown, isoform-specific rescue with RNAi-refractory cDNA, polysome analysis, NF-κB/p38 MAPK signaling assays Molecular and cellular biology High 21135123
2011 MKP-1 promotes cytoplasmic translocation of AUF1 in LPS-stimulated macrophages, which in turn destabilizes IL-6, IL-10, and TNF-α mRNAs. AUF1 siRNA in MKP-1 WT macrophages significantly delays degradation of these cytokine mRNAs, and AUF1 binds these target mRNAs in macrophage lysates. Overexpression of MKP-1, AUF1 siRNA knockdown, mRNA half-life measurements, RIP, Western blot/immunofluorescence for localization Cytokine Medium 21733716
2011 Phosphomimetic mutants of Hsp27 promote proteasome-dependent proteolysis of AUF1, thereby stabilizing ARE-mRNAs. This establishes a p38 MAPK-MK2-Hsp27 signaling axis that targets AUF1 destruction by proteasomes to promote ARE-mRNA stabilization. Hsp27 phosphomimetic mutant overexpression, proteasome inhibitor assays, AUF1 protein stability measurements, ARE-mRNA reporter assays Molecular and cellular biology Medium 21245386
2012 AUF1 directly binds the p40 isoform of AUF1 binds EBER1 (EBV noncoding RNA) in vivo predominantly as the p40 isoform, as shown by UV crosslinking and SILAC mass spectrometry. EBER1 competes with ARE-containing mRNA for AUF1 p40 binding, potentially disrupting normal AUF1/ARE-mRNA homeostasis in EBV-infected cells. MS2-aptamer RNA pulldown with SILAC mass spectrometry, UV crosslinking, EMSA competition assay RNA (New York, N.Y.) High 23012480
2012 AUF1 associates with DICER1 mRNA (both coding region and 3'-UTR) and lowers its stability; AUF1 silencing lengthens DICER1 mRNA half-life and increases Dicer expression, while AUF1 overexpression reduces Dicer, thereby globally reducing mature miRNA levels without affecting pre-miRNA levels. RIP, mRNA half-life assays, AUF1 siRNA KD and overexpression, miRNA northern/qPCR Nucleic acids research High 23066106
2013 AUF1 is a negative regulator of enterovirus (poliovirus, coxsackievirus, human rhinovirus) infection. All four AUF1 isoforms bind stem-loop IV of the poliovirus 5' NCR; viral proteinase 3CD cleavage inhibits this interaction. Viral protein 2A drives cytoplasmic relocalization of AUF1 during infection. AUF1 inhibits viral translation and reduces overall viral titers. In vitro binding assays with purified isoforms, immunofluorescence localization in infected cells, AUF1 overexpression/KD with viral titer assays, proteinase cleavage assay Journal of virology High 23903828
2013 β-TrCP (the substrate recognition subunit of SCF E3 ubiquitin ligase) targets AUF1 for ubiquitination and proteasomal degradation. Depletion of β-TrCP stabilizes AUF1; β-TrCP overexpression enhances AUF1 ubiquitination and degradation, stabilizing cytokine ARE-mRNAs. Enhanced AUF1 degradation requires phosphomimetic mutants of both Hsp27 and AUF1. siRNA depletion of β-TrCP, β-TrCP overexpression, ubiquitination assays, ARE-mRNA reporter stability assays Molecular and cellular biology Medium 23530064
2013 During Coxsackievirus B3 infection, viral protease 2A drives cytoplasmic redistribution of AUF1, and viral protease 3C cleaves AUF1 in vitro. AUF1 knockdown facilitates viral RNA, protein, and progeny production; AUF1 physically interacts with the 3'-UTR of CVB3 genome RNA, targeting it for degradation. In vitro cleavage assay, immunoprecipitation, siRNA knockdown, viral titer and RNA quantification, immunofluorescence FASEB journal Medium 23572232
2014 PAR-CLIP analysis reveals AUF1 primarily recognizes U-/GU-rich sequences in mRNAs and ncRNAs. AUF1 (1) lowers steady-state levels of numerous target RNAs including lncRNA NEAT1, affecting nuclear paraspeckle organization; (2) promotes translation of many target mRNAs without changing their abundance (ribosome profiling); (3) enhances steady-state levels of mRNAs encoding DNA-maintenance proteins. Through these actions, AUF1 preserves genomic integrity and prevents premature cellular senescence. PAR-CLIP, ribosome profiling, RNA-seq, knockdown with cellular phenotype assays (senescence, DNA damage markers) Nature communications High 25366541
2014 AUF1 p45 has RNA chaperone activity that aids structural rearrangement and cyclization of West Nile virus RNA, which is required for the viral replicase to initiate RNA replication. AUF1 p45 specifically supports WNV replication more than other isoforms. In vitro RNA structure assays, cell-based viral replication assays with isoform-specific expression, RNA cyclization assays Journal of virology High 25078689
2014 AUF1 binds to oxidized RNA (containing 8-oxo-7,8-dihydroguanine) specifically and is involved in elimination of oxidatively damaged mRNA in human cells. AUF1-deficient HeLa and Nalm-6 cells show growth retardation and accumulate higher levels of oxidized mRNA. AUF1 knockout by gene targeting (two different methods), oxidized RNA binding assay, mRNA stability measurements with H2O2 treatment Free radical biology & medicine Medium 25486179
2014 AUF1 contributes to cryptochrome 1 (Cry1) mRNA decay and rhythmic translation. AUF1 directly binds the Cry1 3'UTR, interacts with eIF3B and ribosomal proteins S3 and S14, and facilitates translation of Cry1 mRNA in a 3'UTR-dependent manner. Cytoplasmic AUF1 abundance and its binding to the Cry1 3'UTR parallel the circadian CRY1 protein profile. RNA-protein interaction assays (RIP, in vitro binding), co-immunoprecipitation of ribosomal components, reporter assays, circadian expression profiling Nucleic acids research Medium 24423872
2015 AUF1 (p37 isoform) promotes loading of let-7b microRNA onto Argonaute 2 (AGO2); p37 has high affinity for let-7b (Kd ~6 nM). Single-molecule binding analysis shows AUF1 slows assembly of AGO2-let-7b-mRNA complex, yet AUF1 promotes AGO2-let-7-triggered target mRNA decay globally. RNP immunoprecipitation, in vitro binding assays, single-molecule analysis, fluorescence anisotropy (Kd measurement), siRNA depletion Genes & development High 26253535
2016 AUF1-mediated targeted mRNA decay regulates adult muscle satellite cell fate; Auf1(-/-) mice show accelerated skeletal muscle wasting and impaired repair. AUF1 promotes decay of MMP9 mRNA (among other ARE-mRNAs) in satellite cells; secreted MMP9 degrades the skeletal muscle matrix, preventing regeneration. Blocking MMP9 activity in auf1(-/-) mice restores muscle repair and satellite cell population maintenance. AUF1 knockout mouse model, satellite cell mRNA profiling, in vivo muscle injury/regeneration assays, MMP9 inhibitor rescue Cell reports High 27452471
2018 AUF1 p45 supports dengue virus and Zika virus replication as a general flavivirus host factor by RNA chaperone activity. AUF1 p45 destabilizes both the 3'-terminal stem-loop (3'SL) and 5'-terminal SLB to expose UAR cyclization elements, facilitating genome cyclization and enabling viral RdRp to initiate RNA synthesis, without affecting the promoter SLA. In vitro RNA structure analysis (SHAPE, enzymatic/chemical probing), cell-based viral replication assays, isoform-specific expression Journal of virology High 29263261
2018 FBXW7 (E3 ubiquitin ligase) is responsible for protein degradation of AUF1 during ferroptosis. AUF1 antagonizes ferroptosis by up-regulating NRF2 and down-regulating ATF3 (both shown by RIP and mRNA stability assays). AUF1 stabilizes NRF2 mRNA and promotes its expression, while promoting ATF3 mRNA decay. Co-immunoprecipitation, cycloheximide chase analysis, RNA immunoprecipitation, RNA pulldown, mRNA stability assays Cellular and molecular life sciences Medium 35391558
2019 HNRNPD/AUF1 is recruited to DNA double-strand break sites (γH2Ax foci) upon DNA damage. HNRNPD depletion impairs CHK1 S345 phosphorylation, DNA end resection (reduced ssDNA formation, reduced AsiSI-induced DSB resection, reduced RPA32 S4/8 phosphorylation). HNRNPD interacts with SAF-A. HNRNPD depletion causes accumulation of RNA:DNA hybrids (R-loops) at damage sites; expression of RNase H1 or RNA Pol II inhibition rescues the defective DNA damage response. siRNA knockdown, CRISPR/Cas9 KO, in vitro DNA resection assay, immunofluorescence (γH2Ax foci colocalization), ssDNA/RPA assays, RNA:DNA hybrid detection, co-immunoprecipitation with SAF-A Nucleic acids research High 30799487
2019 AUF1 promotes skeletal muscle development and regeneration by stage-specific degradation of fate-determining checkpoint ARE-mRNAs: Twist1 mRNA decay promotes myoblast development; CyclinD1 mRNA decay blocks proliferation and initiates differentiation; RGS5 mRNA decay activates Sonic Hedgehog-mediated differentiation. CTCF activates Auf1 transcription upon satellite cell activation. AUF1 KO mice, satellite cell explant analysis, mRNA decay assays for specific targets, transcriptomic profiling at each myogenic stage 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 competes with p21 (CDKN1A) mRNA for AUF1 binding. Overexpression of circPCNX reduces AUF1 binding to p21 mRNA, stabilizing it and increasing p21 protein production to suppress cell proliferation. Deletion of the AUF1-binding region of circPCNX abrogates p21 elevation and rescues proliferation. RNP immunoprecipitation (RIP), circPCNX overexpression/silencing, p21 mRNA stability assays, deletion mutant analysis of AUF1-binding region Nucleic acids research High 33444453

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1. Molecular and cellular biology 501 8246982
2004 Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs. The EMBO journal 412 15257295
1998 Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms. Genomics 228 9521873
2006 Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes & development 178 17085481
2010 The role of AUF1 in regulated mRNA decay. Wiley interdisciplinary reviews. RNA 160 21956942
2007 Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nature structural & molecular biology 156 17486099
2020 Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Molecular cancer 151 32020881
2014 PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nature communications 144 25366541
2006 Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1. Molecular and cellular biology 130 16954375
2002 A new player in oncogenesis: AUF1/hnRNPD overexpression leads to tumorigenesis in transgenic mice. Cancer research 130 11888925
1996 Regulation of the mRNA-binding protein AUF1 by activation of the beta-adrenergic receptor signal transduction pathway. The Journal of biological chemistry 123 8626551
2003 Selective degradation of AU-rich mRNAs promoted by the p37 AUF1 protein isoform. Molecular and cellular biology 119 12944492
2010 HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology 115 20102719
2000 Differential expression and localization of the mRNA binding proteins, AU-rich element mRNA binding protein (AUF1) and Hu antigen R (HuR), in neoplastic lung tissue. Molecular carcinogenesis 102 10900464
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
2015 Linc-RoR promotes c-Myc expression through hnRNP I and AUF1. Nucleic acids research 98 26656491
2022 AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3. Cellular and molecular life sciences : CMLS 90 35391558
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 85 27620010
2014 Physiological networks and disease functions of RNA-binding protein AUF1. Wiley interdisciplinary reviews. RNA 83 24687816
1997 Structural determinants in AUF1 required for high affinity binding to A + U-rich elements. The Journal of biological chemistry 81 9346902
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
2012 AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein-Barr virus. RNA (New York, N.Y.) 72 23012480
2021 AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production. Nucleic acids research 71 33444453
2008 Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. The Journal of investigative dermatology 70 18830269
2018 Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging 68 30026406
2006 Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. RNA (New York, N.Y.) 66 16556936
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
2008 Identification of a signature motif in target mRNAs of RNA-binding protein AUF1. Nucleic acids research 63 19033365
2019 Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 62 31665914
2011 Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1. Frontiers in bioscience (Landmark edition) 62 21622178
1998 Developmental expression of AUF1 and HuR, two c-myc mRNA binding proteins. Oncogene 61 9692549
2012 RNA-binding protein AUF1 represses Dicer expression. Nucleic acids research 60 23066106
2000 Regulation of the Epstein-Barr virus C promoter by AUF1 and the cyclic AMP/protein kinase A signaling pathway. Journal of virology 59 10933728
2014 MicroRNA-141 and microRNA-146b-5p inhibit the prometastatic mesenchymal characteristics through the RNA-binding protein AUF1 targeting the transcription factor ZEB1 and the protein kinase AKT. The Journal of biological chemistry 58 25261470
2013 Cellular mRNA decay protein AUF1 negatively regulates enterovirus and human rhinovirus infections. Journal of virology 57 23903828
2012 Sequence requirements for RNA binding by HuR and AUF1. Journal of biochemistry 55 22368252
2002 Alternate exon insertion controls selective ubiquitination and degradation of different AUF1 protein isoforms. Nucleic acids research 54 12136087
2010 Alternatively expressed domains of AU-rich element RNA-binding protein 1 (AUF1) regulate RNA-binding affinity, RNA-induced protein oligomerization, and the local conformation of bound RNA ligands. The Journal of biological chemistry 53 20926381
2002 Identification of a novel AU-rich-element-binding protein which is related to AUF1. The Biochemical journal 53 12086581
2019 Depletion of the RNA binding protein HNRNPD impairs homologous recombination by inhibiting DNA-end resection and inducing R-loop accumulation. Nucleic acids research 52 30799487
2011 Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation. Molecular and cellular biology 52 21245386
1999 Regulation of AUF1 expression via conserved alternatively spliced elements in the 3' untranslated region. Molecular and cellular biology 52 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 51 30681073
2022 E2F1-mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10. Cancer science 49 35178834
2014 Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells. Free radical biology & medicine 49 25486179
2015 Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis. Molecular human reproduction 48 26433194
2003 Identification and characterization of proteins that selectively interact with isoforms of the mRNA binding protein AUF1 (hnRNP D). Biological chemistry 48 12674497
2001 Structural remodeling of an A + U-rich RNA element by cation or AUF1 binding. The Journal of biological chemistry 46 11514570
2015 AUF1 promotes let-7b loading on Argonaute 2. Genes & development 45 26253535
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
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
2006 14-3-3sigma is a p37 AUF1-binding protein that facilitates AUF1 transport and AU-rich mRNA decay. The EMBO journal 41 16902409
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
2016 Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity. Cell reports 40 27452471
2010 RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IkappaB kinase complex in monocytes. Molecular and cellular biology 39 21135123
2000 Synchronous and regulated expression of two AU-binding proteins, AUF1 and HuR, throughout murine development. Oncogene 39 11103939
1998 The human HNRPD locus maps to 4q21 and encodes a highly conserved protein. Genomics 39 9615222
2013 Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs. Nucleic acids research 38 23303783
2013 p16(INK4A) positively regulates p21(WAF1) expression by suppressing AUF1-dependent mRNA decay. PloS one 37 23894605
1994 Characterization of cDNAs encoding the murine A+U-rich RNA-binding protein AUF1. Gene 37 7959009
2006 AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1 mRNA stability. Molecular and cellular biology 36 17030625
2001 Structure of the C-terminal RNA-binding domain of hnRNP D0 (AUF1), its interactions with RNA and DNA, and change in backbone dynamics upon complex formation with DNA. Journal of molecular biology 34 11531333
2016 Autotaxin Expression Is Regulated at the Post-transcriptional Level by the RNA-binding Proteins HuR and AUF1. The Journal of biological chemistry 32 27784781
2014 AUF1 contributes to Cryptochrome1 mRNA degradation and rhythmic translation. Nucleic acids research 32 24423872
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
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 29 37589744
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
2021 Tocilizumab suppresses the pro-carcinogenic effects of breast cancer-associated fibroblasts through inhibition of the STAT3/AUF1 pathway. Carcinogenesis 28 34718441
2018 The Host Factor AUF1 p45 Supports Flavivirus Propagation by Triggering the RNA Switch Required for Viral Genome Cyclization. Journal of virology 28 29263261
2013 Hsp27 and F-box protein β-TrCP promote degradation of mRNA decay factor AUF1. Molecular and cellular biology 28 23530064
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
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 27 31113881
2010 Leukotriene B(4) BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway. The Journal of biological chemistry 27 20489206
2008 Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1. The Journal of biological chemistry 27 19074427
2002 Cell death inhibiting RNA (CDIR) derived from a 3'-untranslated region binds AUF1 and heat shock protein 27. The Journal of biological chemistry 27 12356764
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
2012 AUF1/hnRNP D represses expression of VEGF in macrophages. Molecular biology of the cell 24 22379108
2009 The role of AUF1 in thyroid carcinoma progression. Endocrine-related cancer 24 19574297
2019 Helicobacter pylori inhibits GKN1 expression via the CagA/p-ERK/AUF1 pathway. Helicobacter 23 31657090
2006 JNK activation decreases PP2A regulatory subunit B56alpha expression and mRNA stability and increases AUF1 expression in cardiomyocytes. American journal of physiology. Heart and circulatory physiology 23 16603688
2010 Hydrogen peroxide induces p16(INK4a) through an AUF1-dependent manner. Journal of cellular biochemistry 22 20069554
2018 RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1 in hepatocellular carcinoma. Oncotarget 21 29599909
2018 Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for p63α Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell Tumorigenicity. Molecular and cellular biology 21 30104251
2016 Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP). Gene 21 27836661
1999 Characterization of the binding of the RNA-binding protein AUF1 to the human AT(1) receptor mRNA. Biochemical and biophysical research communications 21 10600550
2015 RNA-binding Protein Immunoprecipitation (RIP) to Examine AUF1 Binding to Senescence-Associated Secretory Phenotype (SASP) Factor mRNA. Bio-protocol 20 27453911
2021 SChLAP1 contributes to non-small cell lung cancer cell progression and immune evasion through regulating the AUF1/PD-L1 axis. Autoimmunity 19 33904361
2007 Involvement of RNA binding proteins AUF1 in mammary gland differentiation. Experimental cell research 18 17512931

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