Affinage

HNRNPC

Heterogeneous nuclear ribonucleoproteins C1/C2 · UniProt P07910

Length
306 aa
Mass
33.7 kDa
Annotated
2026-06-10
92 papers in source corpus 28 papers cited in narrative 30 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

HNRNPC is an abundant nuclear RNA-binding protein that recognizes U-rich/poly-uridine tracts in pre-mRNA to govern alternative splicing, alternative cleavage and polyadenylation, miRNA processing, and mRNA stability across diverse cellular programs (PMID:31147722, PMID:34965173, PMID:35729324). It directly binds poly-U motifs in target introns and exons—for example dictating Tau exon 10 inclusion through U-tract recognition that is abolished by motif mutation (PMID:34965173)—and additionally functions as an m6A reader, binding m6A-modified motifs to direct splice-isoform choice and to stabilize target transcripts in a methylation-dependent manner (PMID:34271104, PMID:39921484, PMID:39375330, PMID:38830885). A central biological role is the suppression of endogenous double-stranded RNA: loss of HNRNPC permits accumulation of Alu-derived dsRNA from pre-mRNA introns and unmasking of cryptic splice sites, generating ligands that activate RIG-I and MDA5 type I interferon responses, an effect that synergizes with loss of ADAR-mediated A-to-I editing (PMID:30158112, PMID:34297039). Beyond RNA, HNRNPC restrains innate immune and stress signaling at the protein level by binding and destabilizing p53 under basal conditions and by promoting K48-linked ubiquitination and degradation of the STING/MITA adaptor (PMID:28264987, PMID:39994817). Its abundance and activity are tuned by post-translational modifications—tyrosine phosphorylation reversed by the phosphatase DUSP3, which controls RNA-binding and cytoplasmic IRES-dependent translation (PMID:38538536); lysine 189 crotonylation erased by HDAC3 (PMID:40482911); lysine 176 lactylation that strengthens poly-U binding (PMID:41435694); and ubiquitination by E3 ligases including FBXW11 and a CUL9–p53 complex (PMID:35505093, PMID:41037014). The protein self-assembles into tetramers via a C-terminal domain independent of RNA binding (PMID:23192344). HNRNPC is essential in the male and female germline, where germ-cell-specific knockout causes pachytene meiotic arrest and Sertoli-cell-specific loss disrupts the blood-testis barrier and spermiogenesis (PMID:39921484, PMID:38590182), and HNRNPC dosage controls a neuronal alternative-splicing program required for normal neuronal arborization and migration, with haploinsufficiency linked to a neurodevelopmental/intellectual-disability phenotype (PMID:37541189).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2012 Medium

    Established that hnRNP-C is not merely a monomeric RNA binder but oligomerizes, defining a C-terminal self-assembly module that organizes its activity.

    Evidence in vitro tetramerization and domain mutagenesis with yeast Nab3 functional assays

    PMID:23192344

    Open questions at the time
    • self-assembly characterized largely via the yeast Nab3 ortholog
    • functional consequence of tetramerization for human pre-mRNA targeting not directly tested
    • no structure of the assembled human complex
  2. 2017 Medium

    Showed HNRNPC acts beyond RNA by directly binding and destabilizing p53, positioning it as a basal brake on the apoptotic checkpoint that a competing lncRNA can release.

    Evidence reciprocal Co-IP, RNA pull-down, SNHG1 competition and apoptosis assays after doxorubicin

    PMID:28264987

    Open questions at the time
    • whether p53 destabilization is direct or RNA-bridged not fully resolved
    • single lab
    • physiological contexts of SNHG1 competition undefined
  3. 2018 High

    Identified the key cellular role of HNRNPC in masking intronic Alu-derived dsRNA, preventing aberrant RIG-I interferon activation.

    Evidence siRNA knockdown, dsRNA-IP, RNA-seq and RIG-I reporter assays in two breast cancer lines plus in vivo tumor growth

    PMID:30158112

    Open questions at the time
    • mechanism by which HNRNPC binding prevents duplex formation not structurally defined
    • extent of overlap with other dsRNA-masking factors unclear
  4. 2019 Medium

    Demonstrated HNRNPC regulates alternative polyadenylation site choice, linking its dosage to cancer-associated 3'-end processing programs.

    Evidence subcellular fractionation and APA profiling by RNA-seq in a colon cancer overexpression model

    PMID:31147722

    Open questions at the time
    • direct binding at regulated poly(A) sites not mapped
    • single overexpression model
  5. 2021 Medium

    Extended the dsRNA-suppression model by showing HNRNPC and ADAR act epistatically: their combined loss unmasks cryptic Alu splice sites generating under-edited MDA5 ligands.

    Evidence ADAR/hnRNPC double knockdown, RNA-seq and IFN response assays in THP-1 monocytes

    PMID:34297039

    Open questions at the time
    • relative contribution of editing vs splicing masking to ligand load not quantified
    • single cell system
  6. 2021 High

    Defined the sequence basis of HNRNPC splicing control by mapping poly-U binding to specific Tau introns and showing dose-dependent exon 10 inclusion.

    Evidence RAP-MS, RIP, U-tract mutagenesis and splicing reporter assays

    PMID:34965173

    Open questions at the time
    • splicing mechanism (spliceosome interplay) not detailed
    • relevance to tauopathy in vivo not tested here
  7. 2021 Medium

    Introduced HNRNPC as an m6A-coupled splicing regulator, showing its interaction with target pre-mRNA depends on the m6A mark to bias pro-metastatic isoforms.

    Evidence RIP, m6A-site mutagenesis, splicing and invasion/metastasis assays for TAF8

    PMID:34271104

    Open questions at the time
    • whether HNRNPC reads m6A directly or via an indirect structural switch unresolved
    • single target studied
  8. 2022 High

    Revealed mechanosensitive relocalization of hnRNPC to the sarcomeric Z-disc where it couples to translation and mechanotransduction splicing (YAP1).

    Evidence fractionation, FRAP/live imaging, ribosome association and splicing analysis in mechanically stimulated cardiomyocytes

    PMID:36417487

    Open questions at the time
    • signal driving cytoplasmic Z-disc targeting unknown
    • direct cytoplasmic RNA targets not exhaustively mapped
  9. 2022 Medium

    Established HNRNPC as essential for germ cell support, with Sertoli-cell knockout disrupting cytoskeleton, blood-testis barrier and spermiogenesis.

    Evidence Sertoli-cell conditional knockout mice, RNA-seq, histology, barrier assays

    PMID:38590182

    Open questions at the time
    • RNA targets responsible for barrier/cytoskeleton defects not pinpointed
    • single study
  10. 2022 Medium

    Showed HNRNPC protein level is controlled by a CUL9–p53 ubiquitination axis that tunes ferroptosis sensitivity.

    Evidence Co-IP, ubiquitination assays, CUL9 overexpression and erastin ferroptosis assays in colorectal cells

    PMID:35505093

    Open questions at the time
    • ubiquitination site on HNRNPC not mapped
    • single lab
  11. 2022 Medium

    Broadened HNRNPC's RNA-processing repertoire to miRNA biogenesis, showing poly-U binding near pre-miR-21 reshapes Drosha processing into a cancer-specific isomiR.

    Evidence knockdown, high-throughput sequencing, antagomir and spontaneous liver cancer mouse model

    PMID:35729324

    Open questions at the time
    • direct interaction with Drosha machinery not shown
    • single lab
  12. 2022 Medium

    Identified HNRNPC as a host restriction factor for influenza A, binding the viral NP via its C-terminal auxiliary domain and promoting apoptosis.

    Evidence reciprocal Co-IP across subtypes, domain mapping, viral growth and apoptosis assays

    PMID:36362400

    Open questions at the time
    • mechanism linking NP binding to restriction unclear
    • single lab
  13. 2022 Medium

    Linked HNRNPC to HIF1A mRNA stabilization downstream of IL-6/STAT3, embedding it in a hypoxia/inflammation signaling axis.

    Evidence actinomycin D stability assays, knockdown, rescue and IL-6/STAT3 modulation in HCC cells

    PMID:35848884

    Open questions at the time
    • binding site on HIF1A mRNA not mapped
    • single lab
  14. 2023 Medium

    Established HNRNPC dosage as a determinant of a conserved neuronal splicing program and a neurodevelopmental disease, with both loss and excess impairing neuronal arborization and migration.

    Evidence patient iPSC/fibroblast analysis, RNA-seq meta-analysis across three lines, neuronal assays

    PMID:37541189

    Open questions at the time
    • individual splicing events driving the neuronal phenotype not isolated
    • haploinsufficiency mechanism vs gain-of-function not separated
  15. 2024 Medium

    Defined PTM control of HNRNPC by DUSP3, showing tyrosine dephosphorylation tunes RNA-binding and cytoplasmic IRES-dependent translation of c-MYC and XIAP.

    Evidence DUSP3 knockdown, phosphorylation/polysome profiling, RIP under genotoxic stress

    PMID:38538536

    Open questions at the time
    • kinase responsible for HNRNPC phosphorylation not identified
    • single lab
  16. 2024 Medium

    Consolidated the m6A-reader splicing/stability model across cancers, showing HNRNPC binds m6A-marked FOXM1 and IRAK1 to drive metastatic isoforms and MAPK signaling.

    Evidence RIP, MeRIP-seq, m6A-site mutagenesis and mRNA stability assays in cervical cancer and glioma

    PMID:38830885 PMID:39375330

    Open questions at the time
    • direct m6A recognition vs cooperating reader not resolved
    • each target studied in a single context
  17. 2024 Medium

    Mapped a discrete circRNA interaction interface (residues 16–87) on HNRNPC linked to GPX4/ferroptosis regulation, refining its protein-RNA contact map.

    Evidence RNA pull-down, RIP, mass spectrometry, truncation binding assays in renal cell carcinoma

    PMID:39748364

    Open questions at the time
    • functional contribution of circASAP1 binding to splicing vs sequestration unclear
    • single lab
  18. 2024 Medium

    Showed HNRNPC and UPF1 co-occupy target mRNAs to perform EGF-induced splicing surveillance of proliferation transcripts.

    Evidence irCLIP-RNP and Re-CLIP sequential IP after EGF stimulation (preprint)

    Open questions at the time
    • preprint, not peer-reviewed
    • functional outcome of co-binding on target stability not fully defined
  19. 2024 Medium

    Implicated HNRNPC (with HNRNPA1) as a repressor of TARDBP exitron splicing relevant to TDP-43 proteinopathy, with ASO blockade rescuing neurodegeneration.

    Evidence ASO blockade of binding sites, splicing reporters and TDP-43 mouse model (preprint)

    Open questions at the time
    • preprint, not peer-reviewed
    • relative contributions of HNRNPC vs HNRNPA1 not separated
  20. 2025 Medium

    Demonstrated that distinct acyl-lysine modifications act as functional switches: K189 crotonylation (erased by HDAC3) and K176 lactylation reprogram HNRNPC mRNA stabilization and poly-U binding to drive cancer phenotypes.

    Evidence crotonylome/lactylome MS, site-specific K-to-Q/R mutagenesis, RIP and mRNA stability assays in colorectal and pancreatic cancer

    PMID:40482911 PMID:41435694

    Open questions at the time
    • writers of these acyl marks not all defined
    • interplay between distinct lysine PTMs unexplored
  21. 2025 High

    Defined HNRNPC's in vivo meiotic requirement, showing it cooperates with HuR for m6A-dependent splicing of meiotic genes and that germ-cell knockout arrests meiosis at pachytene in both sexes.

    Evidence germ-cell conditional knockout mice, RIP, m6A-dependent splicing assays, testis histology

    PMID:39921484

    Open questions at the time
    • which specific splicing targets are rate-limiting for meiotic progression not isolated
    • molecular basis of HuR cooperation undefined
  22. 2025 Medium

    Showed HNRNPC suppresses innate antiviral immunity at the protein level by driving K48-ubiquitination and degradation of STING/MITA via its C-terminal domain, an evolutionarily conserved function.

    Evidence Co-IP, K48-ubiquitination assays, zebrafish infection and human HEK293 cells

    PMID:39994817

    Open questions at the time
    • whether HNRNPC recruits an E3 ligase or acts as adaptor not resolved
    • single lab
  23. 2025 Medium

    Identified FBXW11 as an E3 ligase degrading HNRNPC and linked HNRNPC m6A-dependent ACSL3 splicing to placental pathology in preeclampsia.

    Evidence Co-IP, in vitro ubiquitination, m6A-site mutagenesis and mouse preeclampsia model

    PMID:41037014

    Open questions at the time
    • ubiquitination site and degron on HNRNPC not mapped
    • single lab
  24. 2026 High

    Revealed a cell-cycle-regulated rewiring of HNRNPC: during mitosis it shifts density and relocates from introns to 3'UTRs of mature mRNAs to act as a global transcriptome stabilizer.

    Evidence cell-cycle synchronization, fCLIP binding-site mapping, density gradient fractionation and knockdown with global mRNA abundance readout

    PMID:42049236

    Open questions at the time
    • trigger for the mitotic density/binding shift unknown
    • machinery mediating 3'UTR stabilization undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how HNRNPC integrates its many inputs—poly-U recognition, m6A reading, self-assembly state, and a layered PTM code—into context-specific decisions between splicing, polyadenylation, stability, and protein-level regulation of partners like p53 and STING.
  • no integrated structural model of m6A vs poly-U recognition
  • writers/erasers of all PTMs not fully mapped
  • rules governing nuclear splicing vs cytoplasmic translation/stability roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 4 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 3 R-HSA-1474165 Reproduction 2
Partners
CUL9DUSP3FBXW11HURINFLUENZA NPP53STING/MITAUPF1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 HNRNPC repression in breast cancer cells (MCF7, T47D) leads to accumulation of endogenous double-stranded RNA enriched in Alu sequences, predominantly originating from pre-mRNA introns containing HNRNPC binding sites; these dsRNAs activate the RIG-I-mediated interferon response, inhibiting cell proliferation and tumor growth. This establishes HNRNPC's mechanistic role in suppressing endogenous dsRNA formation. siRNA knockdown, RNA-seq, dsRNA immunoprecipitation, RIG-I pathway reporter assays, in vitro and in vivo tumor growth assays The EMBO journal High 30158112
2019 hnRNPC regulates alternative cleavage and polyadenylation (APA) site selection; overexpression of hnRNPC establishes APA profiles characteristic of metastatic colon cancer cells, including regulation of MTHFD1L poly(A) site choice. This was determined by subcellular fractionation to measure nuclear and cytoplasmic APA profiles. Subcellular fractionation, APA profiling by RNA-seq, hnRNPC overexpression in colon cancer cell line model Nucleic acids research Medium 31147722
2017 hnRNPC directly binds p53 protein, destabilizes it, and prevents its activation under normal conditions. Upon doxorubicin treatment, nuclear-retained lncRNA SNHG1 competes with p53 for hnRNPC binding, releasing p53 and promoting p53-dependent apoptosis. Co-immunoprecipitation, RNA immunoprecipitation, RNA pull-down, siRNA knockdown, apoptosis assays, doxorubicin treatment EMBO reports Medium 28264987
2021 HNRNPC antagonizes the anti-metastatic isoform of TAF8 (TAF8L) and promotes the pro-metastatic alternative splicing isoform TAF8S in an m6A-dependent manner; mutation of the m6A site on TAF8 pre-mRNA attenuates HNRNPC-TAF8 interaction, reducing TAF8S production. RNA immunoprecipitation, m6A site mutagenesis, alternative splicing assays, in vitro invasion assays, in vivo metastasis models Cancer letters Medium 34271104
2021 HNRNPC deficiency, synergizing with ADAR loss, leads to dysregulation of Alu-containing introns through unmasked cryptic splice sites, generating putative MDA5 ligands with reduced A-to-I editing, thereby synergistically inducing MDA5-dependent type I IFN responses. Candidate screen in THP-1 monocytes, RNA-seq, ADAR/hnRNPC double knockdown, IFN response assays The Journal of experimental medicine Medium 34297039
2022 hnRNPC is upregulated and relocates to the sarcomeric Z-disc in cardiomyocytes upon pathological extracellular matrix remodeling; at this site it associates with the translation machinery. Changes in hnRNPC expression, phosphorylation, and localization (mechanically determined) affect alternative splicing of mRNAs involved in mechanotransduction, including the Hippo pathway effector YAP1. Subcellular fractionation, immunofluorescence/live imaging, FRAP, hnRNPC overexpression/knockdown, ribosome association assays, alternative splicing analysis, mechanical stimulation of cardiomyocytes Science translational medicine High 36417487
2021 hnRNPC binds poly-uridine (U-tract) sequences in introns 9 and 10 of Tau pre-mRNA; knockdown of hnRNPC induces Tau exon 10 skipping whereas overexpression promotes Tau exon 10 inclusion. Mutation of U-tract motifs abolishes hnRNPC binding and blocks its effect on exon 10 inclusion. RNA Antisense Purification with Mass Spectrometry (RAP-MS), RIP, mutagenesis of U-tract motifs, splicing reporter assays, siRNA knockdown and overexpression RNA biology High 34965173
2023 hnRNPC haploinsufficiency results in altered alternative splicing of multiple intellectual disability-associated genes; a meta-analysis of RNA-seq datasets from three cell lines identified a ubiquitous hnRNPC-dependent alternative splicing signature, confirmed in patient fibroblasts. Either decreased or increased HNRNPC levels impair neuronal arborization and migration. iPSC and fibroblast analysis from individuals with HNRNPC variants, RNA-seq meta-analysis, neuronal arborization and migration assays American journal of human genetics Medium 37541189
2025 hnRNPC works cooperatively with HuR to directly bind and modulate alternative splicing of meiotic-related genes (Sycp1, Brca1, Smc5) in an m6A-dependent manner during spermatogenesis; germ cell-specific knockout of Hnrnpc causes meiotic arrest at the pachytene stage in both male and female mice. Germ cell-specific conditional knockout mice, RNA-seq, RIP, m6A-dependent splicing assays, histological analysis of testes Advanced science High 39921484
2022 hnRNPC induces production of the cancer-specific isomiR-21-5p|±1 in liver cancer by binding upstream of pre-miR-21 via a poly-(U) motif and influencing Drosha processing; this isomiR has a shifted seed sequence that suppresses growth hormone receptor (GHR). High-throughput sequencing analysis, hnRNPC knockdown, antagomir treatment, in vitro tumorigenesis assays, mouse model of spontaneous liver cancer Experimental & molecular medicine Medium 35729324
2024 HNRNPC mediates m6A-dependent alternative splicing of FOXM1 pre-mRNA by binding its m6A-modified motif; mutation of the m6A site on FOXM1 weakens HNRNPC-FOXM1 pre-RNA interaction and reduces the metastasis-promoting FOXM1-S isoform, contributing to lymphatic metastasis in cervical cancer. RIP, m6A site mutagenesis, alternative splicing assays, HNRNPC knockdown/overexpression, migration/invasion assays Cell death & disease Medium 39375330
2022 CUL9 binds p53 and together ubiquitinates HNRNPC for proteasomal degradation; this CUL9-p53-mediated HNRNPC degradation increases resistance to erastin-induced ferroptosis through a CUL9-HNRNPC-MATE1 negative loop in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assays, CUL9 overexpression, siRNA knockdown, ferroptosis assays (erastin treatment), whole genome sequencing Oncogene Medium 35505093
2024 DUSP3 dephosphorylates HNRNPC; DUSP3 knockdown results in tyrosine hyperphosphorylation of HNRNPC, increasing its RNA-binding ability and association with IRES trans-acting factor (ITAF) complexes in the cytoplasm, facilitating translation of IRES-containing mRNAs (c-MYC, XIAP) under genotoxic stress. Hyperphosphorylated HNRNPC also reduces HNRNPC-p53 binding in the presence of RNA. DUSP3 knockdown, phosphorylation assays, polysome profiling, RIP, protein level measurement by western blot, cell synchronization Biology of the cell Medium 38538536
2012 The C-terminal self-assembly domain of hnRNP-C enables it to form tetrameric complexes; this domain is structurally homologous to the yeast Nab3 self-assembly domain. A stretch of 16 glutamines adjacent to a putative α-helix potentiates self-assembly. Self-assembly is independent of RNA binding but acts in concert with RNA interactions. Biochemical self-assembly assays, in vitro tetramerization, domain mutagenesis, yeast functional assays The Journal of biological chemistry Medium 23192344
2022 hnRNPC promotes Sertoli cell function in mice: conditional knockout of hnRNPC in Sertoli cells leads to aberrant proliferation, disrupted cytoskeleton, compromised blood-testis barrier function, and ultimately defective spermiogenesis, establishing an essential role in supporting germ cell development. Conditional knockout mice (Sertoli cell-specific), RNA-seq, histological analysis, blood-testis barrier assays Biology of reproduction Medium 38590182
2022 HNRNPC regulates RhoA as a downstream target; HNRNPC overexpression promotes radiation resistance in pancreatic cancer, and this resistance is attenuated by RhoA silencing. The mechanism involves the RhoA/ROCK2-YAP/TAZ pathway for DNA damage repair and cancer-associated fibroblast activation. siRNA knockdown, HNRNPC overexpression, RhoA inhibition, in vitro radiation resistance assays, in vivo xenograft model Journal of cellular and molecular medicine Low 35277915
2024 HNRNPC stabilizes HIF1A mRNA by directly binding it; HNRNPC downregulation decreases HIF1A expression by destabilizing HIF1A mRNA. Additionally, IL-6/STAT3 signaling upregulates HNRNPC expression in HCC cells. RNA-seq, mRNA stability assays (actinomycin D), HNRNPC knockdown, HIF1A overexpression rescue, IL-6 treatment and STAT3 inhibition Cancer science Medium 35848884
2024 The m6A reader HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the MAPK signaling pathway and malignant behavior in glioma. Integrative RNA-seq and MeRIP-seq identified IRAK1 as a downstream target. RNA-seq, MeRIP-seq, RIP, mRNA stability assays, HNRNPC knockdown/overexpression, IRAK1 knockdown, in vivo glioma models Cell death & disease Medium 38830885
2024 HNRNPC modulates PKM alternative splicing via m6A methylation, upregulating PKM2 expression to promote aerobic glycolysis in papillary thyroid carcinoma. HNRNPC promotes the PKM2 isoform over PKM1 through m6A-dependent splicing regulation. Alternative splicing assays, m6A modification analysis, HNRNPC knockdown, metabolic assays (glycolysis), overexpression studies Journal of translational medicine Low 39380010
2022 hnRNPC interaction with influenza A virus nucleoprotein (NP) is mediated via the C-terminal auxiliary domain of hnRNPC; hnRNPC acts as a negative regulator of influenza viral growth and its interaction with NP promotes host cell apoptosis during viral infection. Co-immunoprecipitation across multiple influenza subtypes, domain mapping (C-terminal auxiliary domain), viral growth assays, apoptosis assays International journal of molecular sciences Medium 36362400
2025 HNRNPC crotonylation at lysine 189 (HNRNPCK189Cr) promotes colorectal cancer cell proliferation by stabilizing CCND1 and MCM3 mRNAs; HDAC3 acts as the specific decrotonylase of HNRNPCK189Cr through the MDM2/HDAC3 axis. Activating (K189Q) and inactivating (K189R) mutations confirmed the functional role of K189 crotonylation. Crotonylome mass spectrometry, HNRNPCK189Q/K189R mutagenesis, HDAC3 agonist treatment, siRNA knockdown, mRNA stability assays, in vivo colorectal cancer models Cancer letters Medium 40482911
2025 HNRNPC lactylation at lysine 176 (K176la) strengthens binding to poly-U motifs in PAK6 pre-mRNA, facilitating expression of the oncogenic isoform PAK6S in pancreatic cancer. Blocking K176la inhibits pancreatic cancer growth and metastasis. Lactylome analysis, HNRNPC K176 mutagenesis, RIP with PAK6 pre-mRNA, alternative splicing assays, in vivo tumor growth models Cancer letters Medium 41435694
2026 During mitosis, hnRNPC undergoes a density shift forming low- and high-density complexes; mitotic hnRNPC acquires prevalent binding to exons, predominantly within 3' UTRs of mature mRNAs (rather than introns as in interphase), acting as a stabilizer of pre-mRNA and mRNA. Downregulation of hnRNPC causes a global negative effect on the abundance of its mitotic targets. Cell cycle synchronization, fCLIP (fluorescent crosslinking immunoprecipitation), RNA-seq, density gradient fractionation, hnRNPC knockdown Nucleic acids research High 42049236
2025 hnRNPC promotes MITA (STING) degradation via K48-linked ubiquitination through its C-terminal domain interaction with MITA, suppressing the type I IFN response. This mechanism is evolutionarily conserved: human hnRNPC similarly interacts with MITA and decreases MITA protein levels in HEK293 cells. Co-immunoprecipitation, ubiquitination assays (K48-linked), hnRNPC overexpression in HEK293 cells, zebrafish model viral infection, IFN production assays Veterinary research Medium 39994817
2025 HNRNPC stabilizes TRAF6 transcripts in an m6A-dependent manner, thereby activating autophagy and driving gemcitabine resistance in pancreatic cancer. Additionally, HNRNPC stabilizes ALDH1A3 mRNA, enhancing glycolysis and H3K18 lactylation, establishing a positive feedback loop where H3K18la drives HNRNPC overexpression. Multi-omics (transcriptomics + epigenomics), mRNA stability assays, m6A-RIP, HNRNPC knockdown, autophagy assays, gemcitabine resistance assays, patient-derived xenograft models Advanced science Medium 41309519
2025 FBXW11 acts as the E3 ubiquitin ligase for HNRNPC, ubiquitinating and degrading HNRNPC in preeclampsia placenta. HNRNPC binds ACSL3 RNA and promotes exon 10 skipping in an m6A-dependent manner; m6A site mutation reduces HNRNPC binding and reduces the ACSL3-S isoform. Co-IP, in vitro ubiquitination assays, western blot, RT-PCR, m6A site mutagenesis, mouse preeclampsia model Journal of hypertension Medium 41037014
2025 HNRNPC m6A reader function regulates the expression of CELF2 through m6A modification; increased HNRNPC in drug-resistant AML cells decreases CELF2 expression, leading to upregulated glycolysis, enhanced glucose consumption, lactate production, and mitochondrial dysfunction. CELF2 knockdown reverses the metabolic effects of HNRNPC knockdown. m6A modification analysis, HNRNPC knockdown/overexpression, CELF2 knockdown/overexpression, metabolic assays (Seahorse XF), glycolysis assays Cell & bioscience Low 40380235
2024 HNRNPC circASAP1 interaction occurs through amino acids 16-87 of HNRNPC (mapped by truncated isoform experiments); HNRNPC binding to circASAP1 influences GPX4-regulated ferroptosis in clear cell renal cell carcinoma. RNA pull-down, RIP, mass spectrometry, truncated HNRNPC isoform binding assays, FISH, GPX4 expression analysis, in vivo tumor models Molecular cancer Medium 39748364
2024 EGF induces recruitment of UPF1 adjacent to HNRNPC on RNA to effect splicing surveillance of cell proliferation mRNAs; simultaneous HNRNPC and UPF1 co-binding was confirmed on RND3 and DDX3X mRNAs by sequential immunoprecipitation. irCLIP-RNP (UV crosslinking IP combined with mass spectrometry), Re-CLIP (sequential immunoprecipitation), EGF stimulation bioRxivpreprint Medium
2024 HNRNPA1 and HNRNPC are key repressors of TARDBP exitron splicing; ASOs blocking their binding sites restored exitron splicing, suppressed TDP-43 pathology and neurodegeneration in neuronal cell models and a mouse model of TDP-43 proteinopathy. ASO-mediated blockade of HNRNPC binding sites, splicing reporter assays, in vitro and in vivo neurodegeneration models bioRxivpreprint Medium

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response. The EMBO journal 164 30158112
2019 hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles. Nucleic acids research 101 31147722
2017 Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions. EMBO reports 91 28264987
2018 MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells. Scientific reports 85 29899543
2022 lncRNA CYTOR promotes aberrant glycolysis and mitochondrial respiration via HNRNPC-mediated ZEB1 stabilization in oral squamous cell carcinoma. Cell death & disease 76 35963855
2021 HNRNPC impedes m6A-dependent anti-metastatic alternative splicing events in pancreatic ductal adenocarcinoma. Cancer letters 75 34271104
2019 LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs. Biochemical and biophysical research communications 60 30824187
2024 CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis. Molecular cancer 58 38184608
2015 HNRNPC as a candidate biomarker for chemoresistance in gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 57 26453116
2017 Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress. Cell death & disease 56 28102850
2023 m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 51 37821382
2022 HNRNPC downregulation inhibits IL-6/STAT3-mediated HCC metastasis by decreasing HIF1A expression. Cancer science 48 35848884
2021 Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression. Journal of translational medicine 48 34952600
2022 LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. Journal of experimental & clinical cancer research : CR 45 36471363
2025 circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4. Molecular cancer 41 39748364
2022 LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2. Cell death & disease 36 36418856
2019 N6-Methyladenosine detected in RNA of testicular germ cell tumors is controlled by METTL3, ALKBH5, YTHDC1/F1/F2, and HNRNPC as writers, erasers, and readers. Andrology 36 30903744
2023 HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer. Cancer science 32 36718950
2023 HNRNPC promotes collagen fiber alignment and immune evasion in breast cancer via activation of the VIRMA-mediated TFAP2A/DDR1 axis. Molecular medicine (Cambridge, Mass.) 31 37528369
2022 Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer. Oncogene 30 35505093
2024 TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization. Cancer letters 28 39102940
2023 Circular RNA circ-FIRRE interacts with HNRNPC to promote esophageal squamous cell carcinoma progression by stabilizing GLI2 mRNA. Cancer science 28 37417427
2022 The mechanical regulation of RNA binding protein hnRNPC in the failing heart. Science translational medicine 28 36417487
2023 LncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC. Journal of ovarian research 27 36805799
2022 Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC. Molecular therapy. Nucleic acids 26 35614994
2021 ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses. The Journal of experimental medicine 26 34297039
2024 The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway. Cell death & disease 25 38830885
2022 HNRNPC regulates RhoA to induce DNA damage repair and cancer-associated fibroblast activation causing radiation resistance in pancreatic cancer. Journal of cellular and molecular medicine 25 35277915
2022 hnRNPC induces isoform shifts in miR-21-5p leading to cancer development. Experimental & molecular medicine 25 35729324
2023 Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease. Pharmacological research 22 37729957
2025 hnRNPC Functions with HuR to Regulate Alternative Splicing in an m6A-Dependent Manner and is Essential for Meiosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 39921484
2018 Friend and foe, HNRNPC takes on immunostimulatory RNAs in breast cancer cells. The EMBO journal 19 30389667
2023 HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder. American journal of human genetics 18 37541189
2024 Cancer-derived exosomal lncRNA SNHG3 promotes the metastasis of colorectal cancer through hnRNPC-mediating RNA stability of β-catenin. International journal of biological sciences 17 38725844
2024 HNRNPC mediates lymphatic metastasis of cervical cancer through m6A-dependent alternative splicing of FOXM1. Cell death & disease 17 39375330
2021 Influence of N6-Methyladenosine Modification Gene HNRNPC on Cell Phenotype in Parkinson's Disease. Parkinson's disease 17 34966539
2012 Yeast Nab3 protein contains a self-assembly domain found in human heterogeneous nuclear ribonucleoprotein-C (hnRNP-C) that is necessary for transcription termination. The Journal of biological chemistry 17 23192344
2022 hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3. BioMed research international 14 35355828
2021 Identification of HnRNPC as a novel Tau exon 10 splicing factor using RNA antisense purification mass spectrometry. RNA biology 14 34965173
2024 HNRNPC modulates PKM alternative splicing via m6A methylation, upregulating PKM2 expression to promote aerobic glycolysis in papillary thyroid carcinoma and drive malignant progression. Journal of translational medicine 12 39380010
2023 Case report: Identification of a novel HNRNPC::RARG fusion in acute promyelocytic leukemia lacking RARA rearrangement. Frontiers in oncology 12 36713535
2022 Serum-derived extracellular vesicles promote the growth and metastasis of non-small cell lung cancer by delivering the m6A methylation regulator HNRNPC through the regulation of DLGAP5. Journal of cancer research and clinical oncology 12 36175801
2024 HNRNPC promotes estrogen receptor-positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A-dependent manner. Molecular carcinogenesis 11 38353359
2025 HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia. Blood 10 40435411
2022 Circ_0022340 promotes colorectal cancer progression via HNRNPC/EBF1/SYT7 or miR-382-5p/ELK1 axis. Cellular and molecular biology (Noisy-le-Grand, France) 10 36495510
2024 Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying Circ-Tulp4 Attenuate Diabetes Mellitus with Nonalcoholic Fatty Liver Disease by Inhibiting Cell Pyroptosis through the HNRNPC/ABHD6 Axis. Tissue engineering and regenerative medicine 9 39546192
2023 N6-methylation of RNA-bound adenosine regulator HNRNPC promotes vascular endothelial dysfunction in type 2 diabetes mellitus by activating the PSEN1-mediated Notch pathway. Diabetes research and clinical practice 9 36681355
2024 N6-Methyladenosine reader HNRNPC-mediated downregulation of circITCH prevents miR-224-3p sequestering and contributes to tumorigenesis in nasopharyngeal carcinoma. Environmental toxicology 7 38299319
2022 Identification and Validation of Three m6A Regulators: FTO, HNRNPC, and HNRNPA2B1 as Potential Biomarkers for Endometriosis. Genes 7 36672827
2024 Role of Circular RNA MMP9 in Glioblastoma Progression: From Interaction With hnRNPC and hnRNPA1 to Affecting the Expression of BIRC5 by Sequestering miR-149. Journal of molecular recognition : JMR 6 39401767
2023 The MYC-Regulated RNA-Binding Proteins hnRNPC and LARP1 Are Drivers of Multiple Myeloma Cell Growth and Disease Progression and Negatively Predict Patient Survival. Cancers 6 38067212
2022 Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma. Journal of oncology 6 35502201
2024 Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC. Digestive diseases and sciences 5 38217675
2024 Sertoli cells require hnRNPC to support normal spermatogenesis and male fertility in mice†. Biology of reproduction 5 38590182
2024 m6A Reader HNRNPC Facilitates Adipogenesis by Regulating Cytoskeletal Remodeling through Enhanced Lcp1 mRNA Stability. Aging and disease 5 38916731
2022 Interaction of Influenza A Nucleoprotein with Host hnRNP-C Is Implicated in Viral Replication. International journal of molecular sciences 5 36362400
2015 Evaluating the role of hnRNP-C and FMRP in the cAMP-induced APP metabolism. BioFactors (Oxford, England) 5 25809670
2025 HNRNPC promotes progression of non-small cell lung cancer by maintaining TFAP2A mRNA stability. Cancer cell international 4 40057699
2025 The m6A reader HNRNPC is a key regulator in DSS-induced colitis by modulating macrophage phenotype. iScience 4 40124522
2025 HNRNPC Promotes Keloid Progression by Modulating the Stability of N6-Methyladenosine-Modified WDR77 mRNA and Expression of TGF-β and SMAD3. The Journal of investigative dermatology 4 40484365
2025 HnRNPC triggers the degradation of MITA to suppress the interferon-mediated antiviral response. Veterinary research 3 39994817
2025 HNRNPC stabilizes m6A-modified AC145207.5 to accelerate tumorigenesis in colorectal cancer by impeding the Nrf2/GPX4 axis-mediated ferroptosis. Non-coding RNA research 3 40290566
2025 The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia. Cell & bioscience 3 40380235
2025 Gobal crotonylome reveals that HNRNPC and its crotonylation promote p53-deficient tumor growth by stabilizing CCND1 and MCM3 mRNAs. Cancer letters 3 40482911
2025 HNRNPC-Mediated m6A Epitranscriptomics Drives CD80-Dependent Tubular Dysfunction in Sepsis-Induced AKI. Inflammation 3 41199093
2025 Positive Feedback Loop of Histone Lactylation-Driven HNRNPC Promotes Autophagy to Confer Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41309519
2024 HNRNPC Regulates GLUT1/LDHA Pathway by Stabilizing FOXM1 mRNA to Promote the Progression and Aerobic Glycolysis of Multiple Myeloma. Annals of clinical and laboratory science 3 38514068
2024 DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus. Biology of the cell 3 38538536
2024 HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation. Oncology research 3 39735682
2022 circXRCC5 foster gastric cancer growth and metastasis by the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 positive feedback loop. Cancer gene therapy 3 35661832
2025 RALYL Overexpression Suppresses Colorectal Cancer via Modulating HNRNPC-Mediated MNK2 Alternative Splicing. Cancer reports (Hoboken, N.J.) 2 40052233
2025 Novel RNA-methylase HNRNPC promotes gastric cancer tumorigenesis by triggering the lactate-induced ferroptosis resistance. Frontiers in immunology 2 40977716
2024 LncRNA LINC00173 inhibits the development of endometrial cancer by interacting with HNRNPC. Translational oncology 2 39191140
2024 Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma. Frontiers of medicine 2 39455467
2023 HNRNPC mediated m6A methylation of 5-methyltetrahydrofolate-homocysteine methyltransferase and involved in the occurrence of RSA. Journal of reproductive immunology 2 37857158
2025 Role of HNF4A-AS1/HNRNPC-mediated HNF4A ubiquitination protection against ritonavir-induced hepatotoxicity. Molecular pharmacology 1 40037142
2025 Long Noncoding RNA CCDC26 Interacts With Vimentin, HNRNPC, CBX1, and CBX5 Proteins in Multiple Intracellular Compartments of Myeloid Leukemia Cells. Genes to cells : devoted to molecular & cellular mechanisms 1 40518278
2025 HNRNPC reprograms cancer metabolism to drive acquired chemoresistance in colorectal cancer by repressing of Nrf2/SLC7A11-dependent ferroptosis. Cell communication and signaling : CCS 1 41366407
2026 [Molecular mechanism of HNRNPC mediated ferroptosis in Ang II-related coronary heart disease]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 41506875
2026 tRF-Gly-CCC-012 enhances malignant process in pancreatic cancer via the HNRNPC/PHGDH axis. Biochemical pharmacology 0 41571199
2026 Dual-targeted NIR-II AIE theranostic nanoparticles disrupt HNRNPC-driven ITGA1+ myCAFs differentiation and immune evasion in oral squamous cell carcinoma. Biomaterials 0 41702227
2026 Targeting circGDI2 disrupt HNRNPC-mediated mPORCN stabilization and enhance LGK-974 anti-tumor therapy in hepatocellular carcinoma. Molecular cancer 0 41808165
2026 Repurposed hnRNPC binds mature mRNAs and safeguards the mitotic transcriptome. Nucleic acids research 0 42049236
2026 YY1 Promotes Diabetic Vascular Calcification Via m6A-Binding Protein HNRNPC. Free radical biology & medicine 0 42191041
2026 CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling. Molecular cancer 0 42210380
2025 The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies. Genes 0 40004505
2025 HNRNPC aggravates the symptoms of preeclampsia by regulating m6A-dependent alternative splicing of ACSL3. Journal of hypertension 0 41037014
2025 HHIPL2 positively governs Hedgehog signaling to accelerate non-small cell lung cancer progression via enhancing HNRNPC-mediated HNF1A mRNA stabilization. Cell death & disease 0 41413056
2025 Unveiling the ZNF384-INTS13-hnRNPC axis as a therapeutic vulnerability in cervical cancer. Cell death & disease 0 41429980
2025 Clinical and Pathologic Description of Three Aneurysmal Bone Cyst Cases With Novel USP6 Fusion Partners Including SEC24D, HNRNPC, and ERRFI1. Genes, chromosomes & cancer 0 41432301
2025 HNRNPC lactylation promotes pancreatic cancer progression through mediating the alternative splicing of PAK6. Cancer letters 0 41435694
2022 Construction and clinical evaluation of N6-methyladenosine risk signature of YTHDC2, IGF2BP2, and HNRNPC in head and neck squamous cell carcinoma. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 0 36416324

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