Affinage

HNRNPH1

Heterogeneous nuclear ribonucleoprotein H · UniProt P31943

Length
449 aa
Mass
49.2 kDa
Annotated
2026-06-10
58 papers in source corpus 36 papers cited in narrative 36 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

HNRNPH1 is a nuclear RNA-binding protein that recognizes G-rich RNA elements to act as a sequence-specific regulator of alternative pre-mRNA splicing across hundreds of targets (PMID:21915099, PMID:17567613, PMID:37248947). Its splicing activity rests on a defined biochemical mechanism: through its qRRM1–qRRM2 domains it binds G-rich sequences with low-nanomolar affinity and non-catalytically destabilizes RNA G-quadruplex (G4) structures, driving the bound RNA toward a non-G4 state that licenses productive splicing decisions, as demonstrated for EWSR1 exon 8 in Ewing sarcoma (PMID:31511320, PMID:35639772). Functionally, it dictates exon inclusion/exclusion outcomes in disease-relevant transcripts including MADD/IG20 and RON in glioblastoma (PMID:21915099), PLP/DM20 in oligodendrocytes (PMID:17567613), OPRM1 in human brain (PMID:25122903), and a cold-responsive RBM3 poison exon whose temperature-dependent skipping it controls via a thermosensitive G-rich interaction (PMID:37248947). HNRNPH1 does not act alone but assembles position-dependent regulatory networks with co-regulators such as PTBP1, PTBP2, SRSF3 and BCAS2, sometimes cooperatively and sometimes competitively, to set splice-site choice (PMID:31391218, PMID:35739118, PMID:36499164, PMID:39520542). A low-complexity LC1 domain drives reversible phase separation that is required for interaction with other RNA-binding proteins and for splicing activity, and this behavior is tuned by post-translational modification: PTK6 phosphorylates HNRNPH1 at Y210 to promote liquid-liquid phase separation and splicing switching, while PRMT1-mediated arginine methylation suppresses its mRNA binding (PMID:34873036, PMID:34027271, PMID:40103198). Beyond splicing, HNRNPH1 participates in nuclear RNA surveillance through an RNA-independent association with the MTR4/MTREX helicase (PMID:34470577), engages transcription factors at gene promoters—AR in Sertoli cells and NRF1 at the DRP1 promoter during mitochondrial retrograde signaling (PMID:36718792, PMID:38898233)—and is essential for germ cell development, where its conditional loss causes aberrant meiotic splicing, blood-testis barrier disruption, and sterility (PMID:35739118, PMID:36718792). In mice, frameshift and 5'UTR variants in Hnrnph1 reduce hnRNP H protein levels and methamphetamine sensitivity through mesolimbic dopaminergic signaling, establishing it as a quantitative trait gene (PMID:26658939, PMID:31704785, PMID:32401417), and HNRNPH1 can functionally substitute for its paralog HNRNPH2 (PMID:37463454).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 High

    Established that hnRNPH directs 5' splice site selection by binding G-rich enhancer elements, defining its core activity as a sequence-specific splicing regulator.

    Evidence siRNA knockdown, G-rich element mutagenesis, and minigene assays on PLP/DM20 in oligodendrocytes

    PMID:17567613

    Open questions at the time
    • Did not resolve structural basis of G-rich recognition
    • Synergy with hnRNPF mechanistically undefined
  2. 2011 High

    Showed hnRNPH-controlled splicing has direct phenotypic consequences in cancer, linking isoform choice to apoptosis and invasion.

    Evidence isoform-specific knockdown and reciprocal rescue of MADD and RON splicing in glioblastoma cells

    PMID:21915099

    Open questions at the time
    • Binding sites on these targets not biophysically mapped
    • Whether effects generalize beyond GBM untested here
  3. 2014 High

    Demonstrated that a human SNP altering hnRNPH binding changes splicing in vivo, connecting the protein's G-rich recognition to genetic variation in human brain.

    Evidence EMSA, minigene, morpholino, and postmortem prefrontal cortex analysis of OPRM1 rs9479757

    PMID:25122903

    Open questions at the time
    • Downstream behavioral/clinical consequence not established
    • Full set of brain targets unknown
  4. 2015 High

    Identified Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity, moving it from a molecular regulator to an organismal behavioral determinant.

    Evidence TALEN frameshift editing with Rufy1 negative control, congenic lines, and behavioral pharmacology in mice

    PMID:26658939

    Open questions at the time
    • Splicing targets mediating dopaminergic effect not pinpointed
    • Causal molecular pathway from gene to behavior incomplete
  5. 2015 Medium

    Placed hnRNPH1 in transcription-factor complexes and androgen signaling, expanding its role beyond splicing into gene-expression control.

    Evidence Co-IP with AR and SRC-3, siRNA knockdown, and prostate tumorigenesis assays

    PMID:26553749

    Open questions at the time
    • Direct vs indirect AR interaction not fully resolved
    • Mechanism of AR-V7 regulation unclear
  6. 2019 High

    Defined the cooperative and competitive logic of hnRNPH1 with other splicing factors, showing position-dependent regulation underlies its target outcomes.

    Evidence minigene, RNA pull-down/EMSA, and knockdown analyses of hnRNPH1/PTBP1 on TCF3 and family-member-specific control of EWSR1 exon 8

    PMID:31391218 PMID:31511320

    Open questions at the time
    • Stoichiometry and spatial arrangement of factors on RNA unresolved
    • Genome-wide cooperativity not yet established
  7. 2019 High

    Linked Hnrnph1 dosage to dopamine release and synaptic mitochondrial protein changes, providing a neurochemical mechanism for the addiction phenotype.

    Evidence operant self-administration, microdialysis, and synaptosomal proteomics in Hnrnph1+/- mice

    PMID:31704785

    Open questions at the time
    • How hnRNP H elevation alters mitochondrial proteins mechanistically unclear
    • Direct splicing targets in striatum unidentified
  8. 2021 Medium

    Identified phase separation of the LC1 domain as the structural basis for hnRNPH1 protein interactions and splicing activity.

    Evidence in vitro droplet assays, domain deletion constructs, and splicing/transcription reporters

    PMID:34873036

    Open questions at the time
    • In vivo relevance of droplets vs polymers not resolved
    • Regulation of phase behavior by signals not addressed here
  9. 2021 Medium

    Extended hnRNPH1 into nuclear RNA surveillance and arginine-methylation control, broadening its mechanistic repertoire.

    Evidence RNA-independent Co-IP with MTR4/MTREX and NEAT1v2/IL8 assays; PRMT1 methylation MS and RIP with hepatocyte PRMT1-KO mice

    PMID:34027271 PMID:34470577

    Open questions at the time
    • Whether MTR4 association is direct unknown
    • Methylated residues and their splicing impact not mapped
  10. 2022 High

    Established the biophysical mechanism of G-quadruplex destabilization and demonstrated an essential germ-cell developmental role with defined splicing co-regulators.

    Evidence biophysical binding/CD/NMR and domain deletions on EWSR1 G4; conditional Hnrnph1 KO with RNA-seq and Co-IP for PTBP2/SRSF3

    PMID:35639772 PMID:35739118

    Open questions at the time
    • Generality of non-catalytic G4 destabilization across targets not proven
    • Sertoli vs germ-intrinsic contributions not separated here
  11. 2023 High

    Revealed hnRNPH1 as a thermosensor for RBM3 splicing and as a dual splicing/transcription regulator partnering AR at promoters in Sertoli cells.

    Evidence genome-wide CRISPR screen in iPSC-neurons with temperature shift for RBM3; conditional Sertoli KO with Co-IP (PTBP1, AR) and ChIP

    PMID:36718792 PMID:37248947

    Open questions at the time
    • Molecular basis of thermosensitive binding unresolved
    • Direct vs cooperative promoter binding mechanism unclear
  12. 2023 High

    Showed HNRNPH1 can functionally compensate for its paralog HNRNPH2, clarifying paralog redundancy in disease models.

    Evidence Hnrnph2 knockin/knockout mouse models with Kapβ2 Co-IP and Hnrnph1 expression quantification

    PMID:37463454

    Open questions at the time
    • Extent of overlapping vs distinct targets between paralogs not defined
    • Compensation mechanism at gene-regulatory level unknown
  13. 2024 Medium

    Connected PTK6 phosphorylation at Y210 to phase separation and a splicing-to-autophagy outcome, and identified hnRNPH1 as a mediator of mitochondrial retrograde signaling.

    Evidence Co-IP, Y210 mutagenesis, FRAP/LLPS, and NBR1 splicing in CRC; subcellular fractionation, NRF1 Co-IP, ChIP on DRP1 promoter and DRP1 Ser616 phosphorylation

    PMID:38898233 PMID:40103198

    Open questions at the time
    • Direct kinase action vs scaffolding for DRP1 not fully separated
    • Link between LLPS state and DRP1 regulation untested
  14. 2024 Medium

    Defined hnRNPH1 as a host factor co-opted by multiple viruses through G4-driven cytoplasmic retention and direct protein interactions affecting innate immunity and viral replication.

    Evidence RNA pull-down, fractionation, IFN reporter, and Co-IP across yellow fever, JEV, and influenza A systems with RRM-domain mutagenesis

    PMID:39094585 PMID:39694377 PMID:39858792

    Open questions at the time
    • Whether antiviral and proviral roles reflect distinct complexes unresolved
    • In vivo relevance of viral hijacking not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HNRNPH1's modular activities—G4 destabilization, phase separation, post-translational tuning, and promoter-level transcription regulation—are integrated to select among hundreds of targets in a given cell state remains unresolved.
  • No unified model linking PTM state to target selectivity
  • Structural basis of cooperativity across multiple G-runs not solved
  • Direct human disease causation by HNRNPH1 mutation not established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1474165 Reproduction 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ARBCAS2MTREXNRF1PTBP1PTBP2PTK6SRSF3
Complex memberships
BCAS2-hnRNPH1-SRSF3 splicing complexhnRNPH1-MTR4/MTREX complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 hnRNPH controls alternative splicing of IG20/MADD (exon 16) and RON (exon 11) pre-mRNAs in glioblastoma, shifting splicing toward anti-apoptotic and pro-invasive isoforms; ablation of hnRNPH increases cell death and reduces invasiveness, phenotypes rescued by isoform-specific knockdown of the respective variants. siRNA knockdown, isoform-specific knockdown, splicing redirection, minigene assays in GBM cell lines The EMBO journal High 21915099
2007 hnRNPH binds G-rich enhancer sequences (M2) in PLP exon 3B and an intronic splicing enhancer (ISE) to promote DM20 5' splice site selection; knockdown of hnRNPH increases the PLP/DM20 ratio in oligodendrocytes, and combined knockdown of hnRNPH and hnRNPF has a synergistic effect mediated through the M2 element. siRNA knockdown in differentiated oligodendrocytes, mutagenesis of G-rich elements, minigene splicing assays, protein binding assays Nucleic acids research High 17567613
2014 hnRNPH binds G-rich sequences at the OPRM1 intronic SNP site (rs9479757); the G-to-A SNP transition weakens hnRNPH binding and causes exon 2 skipping, altering OPRM1 splice-variant mRNA and hMOR-1 protein levels in vitro and in human postmortem prefrontal cortex. EMSA (electrophoretic mobility shift assay), minigene splicing assay, siRNA knockdown, antisense morpholino oligonucleotide studies, human postmortem brain analysis The Journal of neuroscience High 25122903
2015 hnRNPH1 physically interacts with androgen receptor (AR) and steroid receptor coactivator-3 (SRC-3), and regulates expression of AR and its splice variant AR-V7; siRNA silencing of hnRNPH1 reduces AR and AR-V7 expression and sensitizes prostate cancer cells to bicalutamide. Co-immunoprecipitation, siRNA knockdown, ectopic expression of miR-212 mimics, in vivo prostate tumorigenesis assay Clinical cancer research Medium 26553749
2015 TALEN-mediated frameshift deletions in the first coding exon of Hnrnph1 (but not the neighboring gene Rufy1) recapitulate reduced methamphetamine-induced locomotor activity in mice, establishing Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity with a mechanism involving mesolimbic dopaminergic neurotransmission. TALEN gene editing, interval-specific congenic mouse lines, transcriptome analysis (mRNA-seq), behavioral pharmacology PLoS genetics High 26658939
2016 HNRNPH1 (and H2) bind exon 7 of Trf2 pre-mRNA and prevent production of the short TRF2-S isoform; HNRNPH silencing selectively elevates TRF2-S levels during neuronal differentiation, and CRISPR/Cas9-mediated deletion of hnRNPH2 accelerates NGF-triggered neuronal differentiation. Affinity pull-down, siRNA silencing, CRISPR/Cas9 deletion, isoform-specific RT-PCR, NGF differentiation assay Cell reports Medium 27117401
2019 HNRNPH1 (but not other homologous family members) facilitates exclusion of EWSR1 exon 8 from EWS-FLI1 pre-mRNA in Ewing sarcoma cells; this recruitment is driven by guanine-rich sequences within EWSR1 exon 8 capable of folding into RNA G-quadruplex structures, and an RNA G-quadruplex mimetic modulates HNRNPH1 binding and reduces growth of fusion-positive cells. Minigene splicing assay, siRNA knockdown, RNA pull-down, G-quadruplex RNA mimetic binding assay, cell growth assays, pyridostatin treatment RNA (New York, N.Y.) High 31511320
2019 Hnrnph1 heterozygous mutant mice show reduced methamphetamine reinforcement and intake, reduced methamphetamine-induced dopamine release in the nucleus accumbens, and a twofold increase in hnRNP H protein in striatal synaptosomes; synaptosomal proteomics revealed increased baseline mitochondrial complex I and V proteins in H1+/- mice that dynamically changed with methamphetamine administration. Operant self-administration, conditioned place preference, in vivo microdialysis, immunohistochemistry, immunoblot, synaptosomal proteomics (mass spectrometry) The Journal of neuroscience High 31704785
2019 hnRNPH1 and PTBP1 cooperatively regulate TCF3 mutually exclusive alternative splicing: hnRNPH1 binds exonic splicing silencers (ESSs) in exon 18b while PTBP1 binds conserved intronic splicing silencers (ISSs) between the two mutually exclusive exons; position-dependent interactions between these factors are essential for proper MEAS. Minigene splicing assay, siRNA knockdown, RNA pull-down/EMSA for factor binding to ISSs and ESSs RNA (New York, N.Y.) Medium 31391218
2013 hnRNPH1/H2 proteins bind a conserved G-rich sequence element within the U11-48K pre-mRNA and counteract activation of an alternative 3' splice site by U11 snRNP; knockdown of hnRNPH1/H2 or mutation of the G-run enhances 3' splice site activation, revealing a regulatory interplay between hnRNPH1/H2, U1 snRNP, and U11 snRNP. In vitro binding assays, siRNA knockdown, minigene splicing analysis, phylogenetic conservation analysis, mutation of G-run elements RNA (New York, N.Y.) Medium 23335637
2021 The LC1 low-complexity domain of hnRNPH1 undergoes reversible phase separation into polymers or liquid-like droplets, which is critical for interaction with other RNA-binding proteins and for alternative splicing activity; the LC2 domain does not contribute to phase separation but contributes to transcriptional activation when fused to a DNA-binding domain. Phase separation assays (in vitro droplet formation), domain deletion/mutation constructs, splicing reporter assays, transcriptional activation assays Proceedings of the National Academy of Sciences of the United States of America Medium 34873036
2021 hnRNPH1 binds the mRNA of PTPN6 and negatively regulates its expression; hnRNPH1 knockdown in CML cells increases PTPN6 levels, thereby suppressing PI3K/AKT activation and inhibiting cell proliferation while promoting apoptosis. RNA immunoprecipitation/pulldown, siRNA knockdown, western blot, in vitro and in vivo CML cell models Frontiers in oncology Medium 34295818
2021 hnRNPH1 associates with the RNA helicase MTR4/MTREX in an RNA-independent manner and localizes in nuclear speckles; depletion of hnRNPH1 enhances NEAT1v2 stability and promotes NEAT1v2-mediated IL8 mRNA expression, indicating hnRNPH1-MTR4 complex mediates NEAT1v2 degradation to control IL8. Co-immunoprecipitation (RNA-independent), RNA stability assays, siRNA knockdown, nuclear localization (imaging), IL8 mRNA measurement RNA biology Medium 34470577
2022 hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells; conditional knockout of Hnrnph1 in spermatogenic cells causes aberrant splicing of meiosis- and germ-Sertoli communication-related genes, asynapsis of chromosomes, and male and female sterility. Conditional knockout mice, RNA-seq splicing analysis, Co-immunoprecipitation for PTBP2/SRSF3 interaction, histology, fertility assays Nature communications High 35739118
2022 HNRNPH1 binds EWSR1-exon 8 G-rich sequences with low nM affinity and destabilizes G-quadruplex (G4) structures formed by these sequences in a non-catalytic fashion, primarily through its qRRM1-qRRM2 domains; HNRNPH1 associates and dissociates faster from G4-folded RNA than from the same sequences in a non-G4 state, and binding favors accumulation of RNA in a non-G4 state to facilitate splicing regulation. Gel shift assays, spectroscopic assays (CD, NMR-related), biophysical binding measurements, domain-deletion constructs, minigene splicing, long-read sequencing Nucleic acids research High 35639772
2022 SRSF3 and HNRNPH1 competitively bind to PRMT5 pre-mRNA at the region around the 3' splice site on intron 2 and the alternative 3' splice site on exon 4; IR-induced SRSF3 downregulation shifts the competitive balance toward HNRNPH1, increasing the PRMT5-ISO5 isoform level and enhancing tumor radiosensitivity. siRNA silencing of SRSF3 and HNRNPH1, RNA immunoprecipitation, minigene assays, in vivo xenograft irradiation International journal of molecular sciences Medium 36499164
2023 HNRNPH1 mediates cold-dependent skipping of a poison exon in RBM3 pre-mRNA via a thermosensitive interaction with a G-rich motif within the poison exon; moderate hypothermia represses poison exon inclusion in an HNRNPH1-dependent manner, preventing NMD of RBM3 mRNA and enhancing RBM3 protein expression. Genome-wide CRISPR-Cas9 knockout screen in iPSC-derived neurons with RBM3 reporter, splicing analysis, HNRNPH1 knockdown, temperature-shift experiments, minigene assays The EMBO journal High 37248947
2023 hnRNPH1 in Sertoli cells interacts with PTBP1 to regulate alternative splicing of target genes related to cell adhesion, and cooperates with androgen receptor (AR) to directly bind promoters of cell-cell junction and EGFR pathway genes and modulate their transcription; conditional knockout of hnRNPH1 in Sertoli cells disrupts blood-testis barrier, causes meiotic delay, germ cell apoptosis, and infertility. Conditional knockout mice (Sertoli cell-specific), Co-immunoprecipitation (hnRNPH1-PTBP1, hnRNPH1-AR), ChIP (promoter binding), RNA-seq, histology, fertility assays Development (Cambridge, England) High 36718792
2023 Murine knockin models of Hnrnph2 NLS mutations show that these mutations reduce interaction with the nuclear transport receptor Kapβ2 and cause cytoplasmic accumulation of hnRNPH2; Hnrnph2 knockout mice upregulate Hnrnph1 (genetic compensation), whereas knockin mice fail to upregulate Hnrnph1, establishing that HNRNPH1 can functionally substitute for HNRNPH2. Knockin and knockout mouse models, Co-IP for Kapβ2 interaction, immunofluorescence for localization, mRNA/protein quantification, behavioral phenotyping The Journal of clinical investigation High 37463454
2011 hnRNPH1 physically interacts with the mature hepatitis C virus core protein (HCVc174); this interaction was confirmed by pull-down and confocal imaging, and colocalization shifts from cytoplasm+nucleus to cytoplasm only in cells with replicating HCV, indicating active viral replication confines this interaction to the cytoplasm. Affinity purification with LC-MS/MS proteomics, pull-down confirmation, confocal colocalization imaging Journal of proteome research Medium 21823664
2021 PRMT1-mediated arginine methylation of hnRNP H1 suppresses its binding to mRNAs of complement pathway components including C3; PRMT1-dependent methylation requires phosphorylation and reduces complement component expression in vitro; hepatocyte-specific PRMT1 knockout increases complement expression and systemic inflammation in alcohol-fed mice. Mass spectrometry for arginine methylation, RNA immunoprecipitation for mRNA binding, hepatocyte-specific PRMT1 knockout mice, in vitro expression assays Hepatology communications Medium 34027271
2024 PTK6 physically interacts with HNRNPH1 and phosphorylates it at tyrosine Y210, promoting HNRNPH1 liquid-liquid phase separation (LLPS); LLPS of HNRNPH1 triggers splicing-switching of NBR1 exon 10 inclusion, thereby activating autophagy and suppressing apoptosis in colorectal cancer cells. Co-immunoprecipitation, phospho-site mutagenesis (Y210), FRAP, LLPS assays (liquid droplet imaging), minigene/splicing analysis, in vitro kinase assay, PDO and CDX models Autophagy High 40103198
2024 hnRNPH1 functions as a pivotal mediator of mitochondrial retrograde signaling: under mitochondrial stress, hnRNPH1 accumulates in the nucleus via AMPK-dependent mechanism, interacts with transcription factor NRF1, and binds the DRP1 promoter to enhance DRP1 transcription; in the cytoplasm, hnRNPH1 directly interacts with DRP1 and enhances DRP1 Ser616 phosphorylation, triggering DRP1 translocation to mitochondria and mitochondrial fission. Subcellular fractionation, Co-immunoprecipitation, ChIP (DRP1 promoter binding), AMPK inhibition, phospho-specific western blot, mitochondrial morphology imaging Cell death and differentiation Medium 38898233
2024 A conserved G-quadruplex within the polymerase coding region of yellow fever virus (orthoflavivirus) promotes viral replication and suppresses host stress responses via interactions with hnRNPH1; G4 binding to hnRNPH1 causes its cytoplasmic retention, impairing hnRNPH1 control of G4-containing tRNA fragments (tiRNAs) involved in stress-mediated translational reduction, thereby suppressing integrated stress responses and antiviral effects. Yellow fever virus infection, G4 identification, RNA pull-down for hnRNPH1 binding, subcellular fractionation (nuclear vs cytoplasmic localization), stress response assays, tiRNA analysis Cell host & microbe Medium 39094585
2024 HNRNPH1 stabilizes FLOT2 mRNA in an m6A-dependent manner: HNRNPH1 interacts with METTL14 to prevent its STUB1-mediated degradation, leading to increased m6A modification on FLOT2 mRNA; IGF2BP3 then recognizes the m6A modification and further stabilizes FLOT2 mRNA. HNRNPH1 knockdown reduces FLOT2 expression and NPC cell proliferation/invasion. Co-immunoprecipitation (HNRNPH1-METTL14), RNA stability assays, m6A quantification, siRNA knockdown, rescue experiments with METTL14 re-expression, in vitro and in vivo NPC models Cellular oncology Medium 39570559
2024 JEV nonstructural protein NS3 captures HNRNPH1 to recruit poly A-binding protein cytoplasmic 1 (PABPC1) and eukaryotic translation initiation factor 4F (eIF4F) complex, promoting viral replication; HNRNPH1 normally inhibits RIG-I/MDA5 signaling to decrease interferon expression, and SOX10 downregulates HNRNPH1 during JEV infection. Co-immunoprecipitation (NS3-HNRNPH1, HNRNPH1-PABPC1, HNRNPH1-eIF4F), siRNA knockdown, overexpression, IFN reporter assays International journal of biological macromolecules Medium 39694377
2024 hnRNPH1 suppresses influenza A virus (IAV) H1N1 and H9N2 replication by binding viral RNA of PB1, PA, and NP genes through its RRM1 and RRM2 domains and restraining viral polymerase activity; mutation of key tryptophan and tyrosine residues in RRM1 and RRM2 abolishes viral RNA binding and loss of polymerase suppression. Knockdown and overexpression in 293T cells, viral RNA binding assay, polymerase activity assay, site-directed mutagenesis of RRM domains Microorganisms Medium 39858792
2025 HNRNPH1 interacts with IAV NS1 protein via the RBD domain of NS1 and the RRM and NLS regions of hnRNPH1; this interaction changes intracellular localization and splicing function of NS1, and HNRNPH1 interacts with p53 to regulate apoptosis; overexpression of hnRNPH1 decreases IAV multiplication while knockdown enhances replication. Co-immunoprecipitation, domain-mapping experiments (truncation mutants), subcellular localization assay, splicing assay, apoptosis assay, overexpression/knockdown Emerging microbes & infections Medium 40052960
2024 BCAS2, hnRNPH1, and SRSF3 interact to form a complex that orchestrates alternative splicing of Trp53bp1 (53BP1), regulating DNA double-strand break repair during meiotic prophase I; conditional knockout of Bcas2 in germ cells impairs DSB repair and synapsis, and CLIP-seq mapped BCAS2 binding to 5' splice sites and GA-rich regions. Conditional knockout mice, CLIP-seq, Co-immunoprecipitation (BCAS2-hnRNPH1-SRSF3), splicing analysis, DSB repair assays Cellular and molecular life sciences Medium 39520542
2020 Four 5' UTR variants in the DBA/2J allele of Hnrnph1 collectively reduce reporter expression in HEK293 and N2a cells and correspond to decreased 5' UTR usage and reduced hnRNP H protein levels in 114 kb congenic mice striatum, identifying these 5' UTR variants as quantitative trait variants (QTVs) underlying molecular regulation of Hnrnph1. Molecular cloning and reporter assay (5' UTR variants), exon-level transcriptome analysis, immunoblot, congenic mouse lines FASEB journal Medium 32401417
2020 BL-associated TCF3 mutations reduce binding of hnRNPH1 to exon 18b ESS sequences, causing greater exon 18b inclusion and generating more of the mutated E47 isoform; upregulation of E47 dysregulates TCF3 targets PTPN6 and CCND3 involved in BL pathogenesis. RNA pull-down/EMSA (hnRNPH1 binding to WT vs. mutant exon 18b), minigene splicing assays, siRNA knockdown, qRT-PCR for TCF3 targets RNA biology Medium 32449435
2025 HNRNPH1 regulates alternative splicing of EIF4G1 (affecting transcript variants encoding the N-terminus of EIF4G1) and of an AURKA 5'UTR-included exon; reporter constructs show this AURKA 5'UTR exon enhances expression, suggesting HNRNPH1 contributes to regulating AURKA protein levels. HNRNPH1 is identified as a MYCN transcriptional target in neuroblastoma. Short- and long-read RNA-seq after HNRNPH1 depletion, reporter constructs (5'UTR exon), ChIP/expression analysis for MYCN-HNRNPH1 axis bioRxivpreprint Low 40766465
2024 RNA G-quadruplexes mediate cooperative HNRNPH binding: rG4 unfolding by HNRNPH exposes multiple G-rich binding sites, establishing indirect cooperativity that is amplified to achieve switch-like splicing regulation of hundreds of exons; rG4-disrupting variants in tumors alter HNRNPH-dependent splicing patterns in breast cancer. High-throughput in vivo and in vitro binding studies, theoretical modeling of cooperativity, splice event analysis in tumor cohort data bioRxivpreprint Low 41867855
2019 LINC00162 interacts with HNRNPH1 and decreases splicing of the anti-apoptotic BCL-XL variant, increasing sensitivity of gastric cancer cells to 5-aza-dC; knockdown of LINC00162 decreases and overexpression increases 5-aza-dC sensitivity in vitro and in vivo. RNA immunoprecipitation (LINC00162-HNRNPH1 interaction), splicing analysis of BCL-XL, siRNA/overexpression, in vivo tumor model Oncogene Low 30914798
2025 HNRNPH1 interacts with METTL14 to destabilize SPI1 mRNA via the lncRNA lnc-SPI1U; lnc-SPI1U binds HNRNPH1/F and destabilizes SPI1 mRNA, suppressing myeloid differentiation through a PU.1-dependent feedback loop. RNA immunoprecipitation (lnc-SPI1U-HNRNPH1/F), mRNA stability assay, siRNA knockdown/overexpression, ChIP for PU.1 binding Oncogene Low 41136556
2025 HNRNPH1 MACC1 interaction (via MACC1 SH3 domain and HNRNPH1 GYR domain) promotes IRAK1-L long isoform production by preventing the short isoform; HNRNPH1 directly binds the pre-mRNA segment comprising IRAK1 exon 11, bridging MACC1's regulation of IRAK1 splicing in lung adenocarcinoma. Co-immunoprecipitation with domain mapping (SH3/GYR), RNA immunoprecipitation (HNRNPH1 binding to IRAK1 pre-mRNA), splicing analysis (minigene/RT-PCR), siRNA knockdown Journal of cellular physiology Low 39221900

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas. The EMBO journal 138 21915099
2018 Serum exosomal hnRNPH1 mRNA as a novel marker for hepatocellular carcinoma. Clinical chemistry and laboratory medicine 98 29252188
2015 Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 77 26553749
2018 Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion. Haematologica 70 30171027
2007 PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes. Nucleic acids research 66 17567613
2022 hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells. Nature communications 62 35739118
2014 A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the μ opioid receptor gene OPRM1 via hnRNPH interactions. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 25122903
2016 Alternative Splicing of Neuronal Differentiation Factor TRF2 Regulated by HNRNPH1/H2. Cell reports 45 27117401
2015 Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity. PLoS genetics 45 26658939
2019 HNRNPH1-dependent splicing of a fusion oncogene reveals a targetable RNA G-quadruplex interaction. RNA (New York, N.Y.) 44 31511320
2019 A Mutation in Hnrnph1 That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 31704785
2011 Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting partners of the mature hepatitis C virus core protein. Journal of proteome research 39 21823664
2018 Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation. Clinical genetics 36 29938792
2022 HNRNPH1 destabilizes the G-quadruplex structures formed by G-rich RNA sequences that regulate the alternative splicing of an oncogenic fusion transcript. Nucleic acids research 34 35639772
2020 HNRNPH1-related syndromic intellectual disability: Seven additional cases suggestive of a distinct syndromic neurodevelopmental syndrome. Clinical genetics 33 32335897
2023 HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion. The EMBO journal 25 37248947
2013 HnRNPH1/H2, U1 snRNP, and U11 snRNP cooperate to regulate the stability of the U11-48K pre-mRNA. RNA (New York, N.Y.) 25 23335637
2021 Distinct roles of hnRNPH1 low-complexity domains in splicing and transcription. Proceedings of the National Academy of Sciences of the United States of America 24 34873036
2021 HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia. Frontiers in oncology 23 34295818
2019 LncRNA RP11-670E13.6, interacted with hnRNPH, delays cellular senescence by sponging microRNA-663a in UVB damaged dermal fibroblasts. Aging 22 31444317
2018 HNRNPH1 is required for rhabdomyosarcoma cell growth and survival. Oncogenesis 20 29362363
2019 TCF3 mutually exclusive alternative splicing is controlled by long-range cooperative actions between hnRNPH1 and PTBP1. RNA (New York, N.Y.) 19 31391218
2021 HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway. Oncogene 18 34148056
2020 Sex-dependent effects of an Hnrnph1 mutation on fentanyl addiction-relevant behaviors but not antinociception in mice. Genes, brain, and behavior 17 33145940
2019 LINC00162 confers sensitivity to 5-Aza-2'-deoxycytidine via modulation of an RNA splicing protein, HNRNPH1. Oncogene 17 30914798
2025 PTK6 drives HNRNPH1 phase separation to activate autophagy and suppress apoptosis in colorectal cancer. Autophagy 16 40103198
2022 USP36 promotes tumor growth of non-small cell lung cancer via increasing KHK-A expression by regulating c-MYC-hnRNPH1/H2 axis. Human cell 16 35133629
2023 A murine model of hnRNPH2-related neurodevelopmental disorder reveals a mechanism for genetic compensation by Hnrnph1. The Journal of clinical investigation 15 37463454
2022 SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma. International journal of molecular sciences 15 36499164
2021 Hnrnph1 is a novel regulator of alcohol reward. Drug and alcohol dependence 15 33454624
2024 Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control. Cell host & microbe 12 39094585
2023 hnRNPH1 establishes Sertoli-germ cell crosstalk through cooperation with PTBP1 and AR, and is essential for male fertility in mice. Development (Cambridge, England) 12 36718792
2022 A novel HNRNPH1::ERG rearrangement in aggressive acute myeloid leukemia. Genes, chromosomes & cancer 12 35503261
2021 Arginine Methylation of Hepatic hnRNPH Suppresses Complement Activation and Systemic Inflammation in Alcohol-Fed Mice. Hepatology communications 12 34027271
2021 hnRNPH1-MTR4 complex-mediated regulation of NEAT1v2 stability is critical for IL8 expression. RNA biology 12 34470577
2020 5' UTR variants in the quantitative trait gene Hnrnph1 support reduced 5' UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 32401417
2020 Burkitt lymphoma-related TCF3 mutations alter TCF3 alternative splicing by disrupting hnRNPH1 binding. RNA biology 12 32449435
2024 hnRNPH1 maintains mitochondrial homeostasis by establishing NRF1/DRP1 retrograde signaling under mitochondrial stress. Cell death and differentiation 9 38898233
2023 The E3 Ligase TRIM25 Impairs Apoptotic Cell Death in Colon Carcinoma Cells via Destabilization of Caspase-7 mRNA: A Possible Role of hnRNPH1. Cells 7 36611995
2021 Intracranial self-stimulation and concomitant behaviors following systemic methamphetamine administration in Hnrnph1 mutant mice. Psychopharmacology 6 33758972
2025 hnRNPH1: A Multifaceted Regulator in RNA Processing and Disease Pathogenesis. International journal of molecular sciences 5 40507967
2024 Japanese encephalitis virus NS3 captures the protein translation element by interacting with HNRNPH1 to promote viral replication. International journal of biological macromolecules 5 39694377
2025 Eukaryotic RNA binding protein hnRNPH1 suppresses influenza A virus replication through interaction with virus NS1 protein. Emerging microbes & infections 4 40052960
2025 The AhR regulates IFN-induced immune checkpoints in lung cancer cells through HNRNPH1, an RNA-binding protein, and INCR1, a novel long non-coding RNA. The Journal of biological chemistry 4 40449595
2023 In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2. Biomolecules 4 36830718
2022 Variants in HNRNPH1 are associated with high myopia in humans and ocular coloboma in zebrafish. Clinical genetics 4 35989590
2024 MACC1 enhances an oncogenic RNA splicing of IRAK1 through interacting with HNRNPH1 in lung adenocarcinoma. Journal of cellular physiology 3 39221900
2024 HNRNPH1 stabilizes FLOT2 mRNA in a non-canonical m6A-dependent manner to promote malignant progression in nasopharyngeal carcinoma. Cellular oncology (Dordrecht, Netherlands) 3 39570559
2024 hnRNPH1 Inhibits Influenza Virus Replication by Binding Viral RNA. Microorganisms 3 39858792
2025 HNRNPH1 promotes autophagy to inhibit the development of lung adenocarcinoma via the HSP90AB1/MAP1LC3B axis. Respiratory research 2 40468317
2024 BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I. Cellular and molecular life sciences : CMLS 2 39520542
2025 Modulation of Spliceosomal Proteins hnRNPH1 and H2 Increases Melanoma Cell Pro-Inflammatory Signaling In Vitro. Biomolecules 1 41301529
2026 RNA G-quadruplexes mediate cooperativity in HNRNPH binding and splicing regulation. bioRxiv : the preprint server for biology 0 41867855
2026 HNRNPH1 drives glioblastoma progression by regulating the splicing of cell cycle genes. Cell death & disease 0 41872153
2025 [The splicing factor HNRNPH1 regulates Circ-MYOCD back-splicing to modulate the course of cardiac hypertrophy]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 40159973
2025 HNRNPH1-mediated splicing events regulate EIF4G1 transcript variant composition and the organization of the AURKA 5'UTR. bioRxiv : the preprint server for biology 0 40766465
2025 Super-enhancer-associated long noncoding RNA lnc-SPI1U mediates SPI1 feedback regulation by interacting with HNRNPH1 and HNRNPF. Oncogene 0 41136556
2023 Acute Undifferentiated Leukemia With a Balanced t(5;10)(q35;p12) Resulting in Fusion of HNRNPH1 With MLLT10. Cancer genomics & proteomics 0 37400142

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