Affinage

HNRNPAB

Heterogeneous nuclear ribonucleoprotein A/B · UniProt Q99729

Length
332 aa
Mass
36.2 kDa
Annotated
2026-06-10
24 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPAB is a multifunctional RNA-binding protein that acts at multiple post-transcriptional steps—translational repression, mRNA stabilization, and nuclear export—and additionally functions at the transcriptional level by binding gene promoters (PMID:15130489, PMID:15130488, PMID:24146628, PMID:24638979). Its ancestral RNA-handling role is captured by the Drosophila ortholog Hrp48, which binds the 5' and 3' regions of oskar mRNA to enforce translational repression during transport and is independently required for posterior oskar localization via Staufen particle assembly (PMID:15130489, PMID:15130488). In mammals, HNRNPAB directly binds the A2RE/RTS element in the Prm2 3' UTR to impose temporal translational control during spermatogenesis, with isoform partitioning—the p42 isoform associating with translationally active, cap- and polysome-bound Prm2 mRNA and p37 with the repressed pool—such that knockout mice show premature Prm2 translation and abnormal sperm DNA morphology (PMID:24146628). In the nervous system, HNRNPAB controls cortical alternative splicing under cholinergic regulation, governs neural stem cell differentiation, and transcriptionally drives Eps8 to enable neuronal migration from the subventricular zone, a function requiring both p37 and p42 non-redundantly (PMID:22628224, PMID:22332140, PMID:30314980). In cancer, HNRNPAB promotes EMT and metastasis by transcriptionally activating SNAIL1 (repressing E-cadherin) and by binding and stabilizing oncogenic transcripts including MYC, CDK4, CDK1/CDK6, driving proliferation and metastatic phenotypes (PMID:24638979, PMID:38967522, PMID:36657708, PMID:41608617); its abundance is set by ubiquitin-dependent degradation through the E3 ligases ZFP91 and TRIM25, modulated by competing lncRNAs and tRNA-derived fragments that bind HNRNPAB to either promote or block ubiquitination (PMID:33717650, PMID:41144758, PMID:39976282). In antiviral defense, HNRNPAB binds influenza nucleoprotein via a five-residue C-terminal peptide to block the PB1-NP interaction and FluPol assembly, and restricts viral mRNA nuclear export by interfering with the ALY-NXF1 transfer step, with knockout mice showing higher viral burden and mortality (PMID:33681726, PMID:38944160, PMID:34555436).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 High

    Established the ancestral function of this protein family in mRNA handling by showing the ortholog both represses translation of unlocalized mRNA and is independently required for its localization.

    Evidence Drosophila hrp48 genetic alleles, RNA binding assays, and live imaging of GFP-Staufen during oogenesis

    PMID:15130488 PMID:15130489

    Open questions at the time
    • Drosophila ortholog—does not establish human HNRNPAB binding sites or partners
    • Translational repression and localization shown to be separable activities, but molecular basis of each not resolved
  2. 2012 Medium

    Defined HNRNPAB as a regulator of cortical alternative splicing under upstream cholinergic control and linked its loss to dendritic and memory deficits, connecting the protein to neurodegeneration-relevant splicing.

    Evidence hnRNP A/B knockdown in primary neurons and mice, cholinergic neurotoxin lesion, electrocorticography, behavioral testing

    PMID:22628224

    Open questions at the time
    • Specific spliced target transcripts not enumerated
    • Mechanism linking cholinergic signaling to hnRNP A/B level not defined
  3. 2012 Medium

    Showed HNRNPAB controls neural stem cell differentiation and neuronal excitotoxicity sensitivity, and that its nucleocytoplasmic distribution is developmentally regulated.

    Evidence Hnrnpab knockout mouse, neural stem cell culture, glutamate excitotoxicity assay, subcellular fractionation

    PMID:22332140

    Open questions at the time
    • Molecular targets mediating differentiation phenotype unknown
    • Signal controlling nucleocytoplasmic redistribution not identified
  4. 2013 High

    Resolved how HNRNPAB imposes temporal translational control in spermatogenesis through direct 3' UTR element binding and isoform-specific partitioning between repressed and active mRNA pools.

    Evidence RNA-IP, direct binding to A2RE/RTS element, polysome fractionation, cap-complex pulldown, Hnrnpab knockout mouse

    PMID:24146628

    Open questions at the time
    • Structural basis distinguishing p37 vs p42 association not defined
    • Whether the same isoform logic applies to other mRNAs unknown
  5. 2014 Medium

    Identified a transcriptional (rather than purely post-transcriptional) role: HNRNPAB activates SNAIL1 to repress E-cadherin and drive EMT and metastasis.

    Evidence siRNA, overexpression, invasion assays, in vivo lung metastasis model, reporter and ChIP assays in HCC

    PMID:24638979

    Open questions at the time
    • How an RNA-binding protein engages the SNAIL1 promoter mechanistically unclear
    • Cofactors for transcriptional activation not identified
  6. 2018 Medium

    Demonstrated non-redundant cooperation of both isoforms in transcriptional control of Eps8 driving neural migration, extending the transcriptional role to development.

    Evidence Hnrnpab knockout mouse, SVZ migration assay, RNA-seq, isoform re-expression rescue

    PMID:30314980

    Open questions at the time
    • Mechanism requiring both isoforms together not explained
    • Direct promoter occupancy at Eps8 not detailed
  7. 2021 Medium

    Established HNRNPAB as an antiviral restriction factor that blocks influenza viral mRNA nuclear export by interrupting the ALY-NXF1 transfer step in cooperation with viral NP.

    Evidence Co-IP, overexpression/knockdown, nuclear export and binding competition assays; separate study with avian PB2 mRNA and RNA-IP

    PMID:33681726 PMID:34555436

    Open questions at the time
    • Whether restriction reflects host defense or viral hijacking of the protein not fully resolved
    • Direct vs indirect engagement of export machinery not structurally defined
  8. 2021 Medium

    Showed HNRNPAB abundance is set by lncRNA-scaffolded E3 ligase recruitment, defining a degradation mechanism that gates its EMT-driving transcriptional activity.

    Evidence RNA pull-down, Co-IP, ubiquitination assay identifying ZFP91 within an Hsp90α/HNRNPAB complex, peritoneal dissemination model in gastric cancer

    PMID:33717650

    Open questions at the time
    • Ubiquitination acceptor residue for ZFP91 not mapped
    • Generality across tissues unknown
  9. 2024 High

    Mapped the precise interaction interface (C-terminal aa 318-322) by which HNRNPAB blocks PB1-NP binding and FluPol assembly, and confirmed protective antiviral function in vivo.

    Evidence Co-IP, 5-aa domain mapping, viral polymerase activity assay, hnRNPAB knockout mouse influenza infection

    PMID:38944160

    Open questions at the time
    • Relationship between polymerase-assembly block and mRNA-export block not integrated
    • Structure of the HNRNPAB-NP interface not solved
  10. 2024 Medium

    Extended the oncogenic mechanism to mRNA stabilization, showing HNRNPAB prolongs MYC mRNA half-life to drive CXCL8-dependent neutrophil recruitment and liver metastasis.

    Evidence RNA-IP, mRNA half-life measurement, xenograft metastasis model, CXCL8 secretion assay in PDAC

    PMID:38967522

    Open questions at the time
    • RNA element recognized in MYC mRNA not defined
    • Whether stabilization requires a specific isoform unknown
  11. 2023 Medium

    Placed HNRNPAB in a feed-forward proliferative circuit: it is a direct c-Myc transcriptional target that in turn stabilizes CDK4 mRNA to drive G1/S progression.

    Evidence ChIP, luciferase reporter, RIP, flow cytometry, colony formation in lung adenocarcinoma

    PMID:36657708

    Open questions at the time
    • Direct CDK4 mRNA binding site not mapped
    • Isoform dependence not addressed
  12. 2025 Medium

    Defined small-RNA control of HNRNPAB stability, with tRF-22 binding Lys91 to block TRIM25-mediated ubiquitination, stabilizing HNRNPAB to activate TGFB2 transcription and immunosuppression.

    Evidence Residue-level RNA-protein binding, ubiquitination assay, TRIM25 identification, TGFB2 reporter/ChIP, immune infiltration analysis in ESCC

    PMID:41144758

    Open questions at the time
    • Whether Lys91 is the TRIM25 ubiquitination acceptor or only a regulatory site unclear
    • Interplay with ZFP91-mediated degradation not addressed
  13. 2025 Medium

    Linked HNRNPAB degradation to NF-κB/Lcn2 signaling and neuronal ferroptosis, broadening its regulatory reach beyond cancer.

    Evidence RNA pull-down, RIP, Co-IP, K48 ubiquitination assay, signaling western blots, in vivo controlled cortical impact model

    PMID:39976282

    Open questions at the time
    • E3 ligase mediating Ntoco-directed degradation not identified
    • Direct connection between HNRNPAB and NF-κB pathway components not established
  14. 2026 Medium

    Showed HNRNPAB can promote back-splicing of circRNA and couple a circRNA cofactor to mRNA stabilization, integrating circular and linear RNA regulation in cell cycle control.

    Evidence RIP, mRNA stability assay, overexpression/knockdown, flow cytometry in ER+ breast cancer

    PMID:41608617

    Open questions at the time
    • Mechanism of Alu-element-directed back-splicing not detailed
    • Stoichiometry of circESR1-HNRNPAB-CDK mRNA complex not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HNRNPAB switches between repressing translation, stabilizing mRNA, controlling nuclear export, and binding promoters—and what determines this functional partitioning across isoforms, modifications, and subcellular compartments—remains unresolved.
  • No structural model of HNRNPAB on its RNA or promoter targets
  • Rules governing p37 vs p42 functional specialization not unified
  • Mechanism by which an RNA-binding protein engages chromatin/promoters not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140110 transcription regulator activity 4 GO:0045182 translation regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2
Partners
HSP90AA1KAP1NPTRIM25ZFP91

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 hnRNP A/B knockdown in primary neurons induced alternative splicing impairments and dendrite loss, and caused memory and electrocorticographic impairments in mice; cholinergic excitation increased hnRNP A/B levels while neurotoxin-mediated destruction of cholinergic neurons caused cortical decrease in hnRNP A/B and recapitulated AD-like alternative splicing patterns, establishing cholinergic regulation of hnRNP A/B as a mechanism controlling cortical splicing. hnRNP A/B knockdown in primary neurons and mice, in vivo cholinergic neurotoxin lesion, electrocorticography, behavioral memory testing EMBO molecular medicine Medium 22628224
2004 Drosophila hnRNP A/B homolog Hrp48 (ortholog of HNRNPAB) binds to the 5' and 3' regions of oskar mRNA and is required for translational repression of unlocalized oskar mRNA during transport; Hrp48 levels are crucial for polarization of the oocyte during mid-oogenesis. Genetic mutant analysis (three hrp48 alleles), RNA binding assays, oocyte phenotypic analysis Developmental cell High 15130488 15130489
2004 Drosophila Hrp48 colocalizes with oskar mRNA throughout oogenesis and its loss specifically abolishes oskar mRNA posterior localization without affecting translational control, splicing, or other mRNA localizations; Hrp48 mutations disrupt GFP-Staufen particle formation, defining a new step in the localization pathway. Germline clone screen, live imaging of GFP-Staufen, genetic mutant analysis (three missense alleles), RNA localization assays Developmental cell High 15130488 15130489
2013 CBF-A/Hnrnpab directly binds the A2RE/RTS element in the 3' UTR of Protamine2 (Prm2) mRNA and contributes to temporal translational regulation during spermatogenesis; the p42 isoform associates with translationally active (de-repressed) Prm2 mRNA and interacts with the 5' cap complex and polysomes, whereas p37 associates with translationally repressed Prm2 mRNA; Hnrnpab knockout mice show reduced PRM2 expression and premature Prm2 translation with abnormal sperm DNA morphology. RNA immunoprecipitation, direct binding assay, polysome fractionation, 5' cap complex pulldown, Hnrnpab knockout mouse analysis PLoS genetics High 24146628
2014 HNRNPAB transcriptionally activates SNAIL1, which in turn represses E-cadherin transcription, thereby promoting epithelial-mesenchymal transition (EMT) and metastasis of hepatocellular carcinoma; siRNA-mediated silencing of SNAIL attenuated HNRNPAB-enhanced invasion in vitro and lung metastasis in vivo. RNA interference (siRNA), overexpression, in vitro invasion assays, in vivo lung metastasis model, reporter and ChIP assays Cancer research Medium 24638979
2012 Hnrnpab knockout mouse neural stem and progenitor cells undergo altered differentiation patterns; mature Hnrnpab(-/-) neurons show increased sensitivity to glutamate-induced excitotoxicity; Hnrnpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage. Hnrnpab knockout mouse, neural stem cell culture, glutamate excitotoxicity assay, subcellular fractionation/localization RNA (New York, N.Y.) Medium 22332140
2018 Hnrnpab regulates transcription of Eps8 in the subventricular zone; loss of Hnrnpab decreases Eps8 expression and impairs neural cell migration from the SVZ; both alternatively spliced Hnrnpab isoforms (p37 and p42) are required together (non-redundantly) to restore Eps8 transcription and cell motility. Hnrnpab knockout mouse, SVZ migration assay, RNA-seq, ectopic re-expression of individual isoforms RNA (New York, N.Y.) Medium 30314980
2021 hnRNPAB interacts with influenza A virus nucleoprotein (NP) and restricts viral mRNA nuclear export by inhibiting mRNA transfer from ALY to NXF1; NP cooperates with hnRNPAB to interrupt the ALY-UAP56 interaction, repressing ALY-viral mRNA binding and nuclear export of viral mRNA. Co-immunoprecipitation, overexpression/knockdown, nuclear export assays, binding competition assays iScience Medium 33681726
2024 hnRNPAB interacts with influenza A virus NP via a 5-amino-acid peptide at its C-terminal domain (aa 318-322) to inhibit the PB1-NP interaction, thereby disrupting FluPol complex assembly and inhibiting viral polymerase activity; hnRNPAB-deficient mice show higher viral burdens and increased mortality after influenza infection. Co-immunoprecipitation, domain mapping (5-aa peptide), viral polymerase activity assay, hnRNPAB knockout mouse in vivo infection Antiviral research High 38944160
2021 hnRNPAB associates with avian influenza viral PB2 mRNA; overexpression of hnRNPAB reduces PB2 mRNA nuclear export and PB2 protein level (without changing PB2 mRNA level), restricts viral polymerase activity, and inhibits virus replication; virus infection induces nuclear accumulation of hnRNPAB. RNA immunoprecipitation, overexpression/knockdown, mRNA nuclear export assay, viral polymerase activity assay, subcellular fractionation Virus research Medium 34555436
2021 lnc-CTSLP4 binds HNRNPAB within an Hsp90α/HNRNPAB complex and recruits E3-ubiquitin ligase ZFP91 to induce ubiquitination and degradation of HNRNPAB, thereby suppressing HNRNPAB-dependent transcriptional activation of Snail and reversing EMT in gastric cancer cells. RNA pull-down, co-immunoprecipitation, ubiquitination assay, gain/loss-of-function assays, peritoneal dissemination in vivo model Molecular therapy. Nucleic acids Medium 33717650
2025 tRF-22 binds to Lys91 on hnRNPAB and inhibits its ubiquitination by TRIM25, leading to hnRNPAB stabilization; stabilized hnRNPAB activates TGFB2 transcription, which promotes PMN-MDSC generation and immunosuppression in esophageal squamous cell carcinoma. RNA-protein binding assay (residue-level), ubiquitination assay, TRIM25 identification, TGFB2 transcription reporter/ChIP, immune cell infiltration analysis Advanced science Medium 41144758
2024 hnRNPAB binds MYC mRNA and prolongs its half-life (mRNA stabilization), thereby increasing MYC protein levels and downstream CXCL8 secretion, which promotes neutrophil recruitment and facilitates liver metastasis in pancreatic ductal adenocarcinoma. RNA immunoprecipitation, mRNA stability assay (half-life measurement), xenograft metastasis model, CXCL8 secretion assay Molecular cancer research: MCR Medium 38967522
2023 hnRNPAB is a direct transcriptional target of c-Myc (ChIP and luciferase reporter confirmed); hnRNPAB binds CDK4 mRNA and stabilizes it, increasing CDK4 protein levels and promoting G1/S cell cycle progression and lung adenocarcinoma cell proliferation; hnRNPAB mediates the proliferative effect of c-Myc. ChIP, luciferase reporter assay, RNA immunoprecipitation (RIP), flow cytometry, colony formation assay The international journal of biochemistry & cell biology Medium 36657708
2019 HNRNPAB represses transcription of lnc-ELF209 by directly binding to its promoter region, as demonstrated by chromatin immunoprecipitation; lnc-ELF209 in turn inhibits HNRNPAB-promoted HCC cell migration, invasion, and EMT. Chromatin immunoprecipitation (ChIP), lncRNA microarray, qRT-PCR, gain/loss-of-function assays International journal of cancer Medium 31090062
2025 lncRNA Ntoco binds Hnrnpab and facilitates K48-linked ubiquitination and degradation of Hnrnpab, suppressing NF-κB/Lcn2 signaling (reduced IkBα phosphorylation, increased IKKα/β phosphorylation, nuclear translocation of NF-κB p65, elevated Lcn2), thereby promoting ferroptosis in neurons following traumatic brain injury. RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, ubiquitination assay (K48 linkage), western blotting, in vivo CCI mouse model CNS neuroscience & therapeutics Medium 39976282
2025 KAP1 interacts with HNRNPAB as identified by mass spectrometry, further modulating YAP1 signaling in gastric adenocarcinoma. Mass spectrometry (protein interaction), co-immunoprecipitation implied Cancer letters Low 40189014
2026 HNRNPAB promotes back-splicing and expression of circESR1 by binding to Alu elements of cognate ESR1 pre-mRNA; HNRNPAB also binds and stabilizes CDK1 and CDK6 mRNAs, and this stabilization is facilitated by asymmetrical circESR1 binding to HNRNPAB, promoting cell cycle progression in ER+ breast cancer cells. RNA immunoprecipitation, mRNA stability assay, overexpression/knockdown, flow cytometry for cell cycle International journal of biological sciences Medium 41608617
2024 tRFValCAC (a sperm-enriched tRNA fragment) interacts with hnRNPAB in the epididymis, and this interaction regulates sorting and packing of tRFValCAC into extracellular vesicles for delivery to sperm. RNA-protein interaction assay (RNA pull-down/RIP), extracellular vesicle isolation and characterization bioRxivpreprint Low
2026 Overexpression of duck HNRNPAB reduced MAVS-induced IFNβ promoter activity and MAVS protein abundance, identifying HNRNPAB as a negative regulator of MAVS-mediated Type I IFN signaling. Overexpression functional assay, IFNβ promoter reporter assay, western blotting for MAVS abundance Scientific reports Low 41807513

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice. EMBO molecular medicine 139 22628224
2004 Hrp48, a Drosophila hnRNPA/B homolog, binds and regulates translation of oskar mRNA. Developmental cell 101 15130489
2014 HNRNPAB induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by transcriptionally activating SNAIL. Cancer research 96 24638979
2004 The Drosophila hnRNPA/B homolog, Hrp48, is specifically required for a distinct step in osk mRNA localization. Developmental cell 88 15130488
2021 Tumor suppressor lnc-CTSLP4 inhibits EMT and metastasis of gastric cancer by attenuating HNRNPAB-dependent Snail transcription. Molecular therapy. Nucleic acids 34 33717650
2021 Post-Translational Modifications Modulate Proteinopathies of TDP-43, FUS and hnRNP-A/B in Amyotrophic Lateral Sclerosis. Frontiers in molecular biosciences 32 34291086
2013 The transacting factor CBF-A/Hnrnpab binds to the A2RE/RTS element of protamine 2 mRNA and contributes to its translational regulation during mouse spermatogenesis. PLoS genetics 32 24146628
2019 HNRNPAB-regulated lncRNA-ELF209 inhibits the malignancy of hepatocellular carcinoma. International journal of cancer 31 31090062
2012 Hnrpab regulates neural development and neuron cell survival after glutamate stimulation. RNA (New York, N.Y.) 24 22332140
2021 Cellular hnRNPAB binding to viral nucleoprotein inhibits flu virus replication by blocking nuclear export of viral mRNA. iScience 23 33681726
2017 Marek's disease virus type 1 encoded analog of miR-155 promotes proliferation of chicken embryo fibroblast and DF-1 cells by targeting hnRNPAB. Veterinary microbiology 17 28757026
2023 Knockdown of hnRNPAB reduces the stem cell properties and enhances the chemosensitivity of human colorectal cancer stem cells. Oncology reports 10 37165920
2018 Hnrnpab regulates neural cell motility through transcription of Eps8. RNA (New York, N.Y.) 8 30314980
2024 hnRNPAB Promotes Pancreatic Ductal Adenocarcinoma Extravasation and Liver Metastasis by Stabilizing MYC mRNA. Molecular cancer research : MCR 4 38967522
2023 The c-Myc targeting hnRNPAB promotes lung adenocarcinoma cell proliferation via stabilization of CDK4 mRNA. The international journal of biochemistry & cell biology 4 36657708
2025 Ntoco Promotes Ferroptosis via Hnrnpab-Mediated NF-κB/Lcn2 Axis Following Traumatic Brain Injury in Mice. CNS neuroscience & therapeutics 3 39976282
2025 tRNA-Derived Fragment tRF-22 Promotes Immunosuppression by Inhibiting HnRNPAB Ubiquitination in Esophageal Squamous Cell Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41144758
2021 Cellular hnRNPAB interacts with avian influenza viral protein PB2 and inhibits virus replication potentially by restricting PB2 mRNA nuclear export and PB2 protein level. Virus research 3 34555436
2025 KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB. Cancer letters 2 40189014
2024 hnRNPAB inhibits Influenza A virus infection by disturbing polymerase activity. Antiviral research 1 38944160
2026 The Interaction of CircESR1 and HNRNPAB Regulates Cell Cycle Transition of Breast Cancer Cell. International journal of biological sciences 0 41608617
2026 Duck lncRNA lnc455 enhances RIG-I/MAVS type I interferon signaling by modulating hnRNPAB-mediated regulation of MAVS signaling. Scientific reports 0 41807513
2026 Identifying and validating ITGB2 and HNRNPAB as diagnostic biomarkers in chronic obstructive pulmonary disease using bioinformatics and Integrated Machine Learning Methods. PloS one 0 42166424
2025 Mechanism of silica nanoparticles induced pulmonary epithelial-mesenchymal transition mediated by exosomal HNRNPAB. Ecotoxicology and environmental safety 0 41056680

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