Affinage

HNRNPL

Heterogeneous nuclear ribonucleoprotein L · UniProt P14866

Length
589 aa
Mass
64.1 kDa
Annotated
2026-06-10
57 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HNRNPL is a multifunctional CA-rich-element-binding protein that integrates RNA processing with chromatin-based transcriptional control across diverse cell lineages (PMID:31857580, PMID:34543262, PMID:38744970). As a splicing regulator, it recognizes intronic CA-rich elements to direct alternative splicing of specific pre-mRNAs—promoting exon 13 skipping in SLK to generate an oncogenic ERK-activating isoform (PMID:41046074), controlling tropomyosin splicing in cardiac muscle (PMID:39300280), preventing intron retention in FOXO4 (PMID:41530849), and supporting myelin gene (Mag, Nfasc) and histone-modifier (KDM6A, SIRT1) splicing programs that underlie oligodendrocyte differentiation and B cell activation (PMID:38744970, PMID:40930975). In the cytoplasm it binds CA-repeat elements within target transcripts (MTNR1A, S100A9, WSB1, CCL5, CFTR) to stabilize them against exosome- and NMD-mediated decay, thereby tuning downstream signaling, ferroptosis, lipid metabolism, and immune chemoattraction (PMID:32730662, PMID:38368714, PMID:36869127, PMID:38045134). On chromatin, HNRNPL acts as a transcriptional co-activator: it binds gene loci, recruits and stabilizes RNA polymerase II elongation, and forms phase-separated condensates that activate transcription of integrin/ECM genes in epidermal stem cells and PIK3CB in ovarian cancer (PMID:34543262, PMID:40413189). This activity is frequently templated by non-coding RNAs—lncRNAs, enhancer RNAs, and promoter-derived transcripts (THRIL, seRNA-1, lncFAM, CASC8, SNHG1/6, circMGA)—that recruit or sequester HNRNPL at target promoters and modulate its stability and condensation (PMID:24371310, PMID:31857580, PMID:36533518, PMID:35982900, PMID:40413189, PMID:36869127). It also delivers inactive P-TEFb (CDK9/CCNT2/HEXIM1/7SK) to promote Pol II elongation (PMID:24434558) and serves as a structural adaptor bridging RNase-sensitive substructures of the Sam68 nuclear body via its RRMs (PMID:27377249). HNRNPL abundance is governed post-translationally by FBXO16-SCF-mediated ubiquitination and proteasomal degradation through its RRM3 domain (PMID:34333526) and by SENP3-mediated deSUMOylation (PMID:40792025). Through these activities it is essential for B cell germinal-center responses, oligodendrocyte differentiation, epidermal stem cell maintenance, and spermatogenesis (PMID:38744970, PMID:40930975, PMID:34543262, PMID:22245417).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2002 Medium

    First evidence that hnRNP-L participates directly in transcriptional regulation rather than RNA processing alone, by complexing with APE1 at a promoter repressor element.

    Evidence EMSA, UV cross-linking, and co-IP on the nCaRE-B2 element of the APE1 promoter

    PMID:11809897

    Open questions at the time
    • Protein-protein interaction shown but functional transcriptional output not measured genome-wide
    • Single lab, single promoter context
  2. 2009 Medium

    Established hnRNP-L as a host RNA-binding factor that can be co-opted by viral replication complexes, binding HDV genomic RNA.

    Evidence UV cross-linking/MS, RNA affinity chromatography, and co-IP in HeLa cells

    PMID:19464723

    Open questions at the time
    • No functional perturbation of HDV replication shown
    • RNA element binding characterized only in vitro
  3. 2012 High

    Showed hnRNPL restrains genome mobility, acting as a negative regulator of LINE-1 retrotransposition through IRES RNA binding.

    Evidence RNA affinity chromatography, siRNA knockdown, and L1 retrotransposition reporter assay

    PMID:23161687

    Open questions at the time
    • Mechanism by which binding suppresses ORF2 translation/retrotransposition not resolved
    • Endogenous L1 targets not mapped
  4. 2012 Medium

    Identified hnRNPL as a regulator of spermatogenesis with opposing roles in germ versus Sertoli cells.

    Evidence 2D-gel proteomics, MALDI-TOF, and siRNA knockdown in GC-1 and TM4 cells with target validation (CEACAM1, iNOS)

    PMID:22245417

    Open questions at the time
    • Direct RNA targets versus indirect effects not distinguished
    • Cell-type-specific opposing phenotype mechanism unexplained
  5. 2014 High

    Connected hnRNPL to Pol II elongation control by showing it delivers inactive P-TEFb to target loci, linking it to the 7SK snRNP.

    Evidence Genome-scale shRNA screen, co-IP with CDK9/CCNT2/HEXIM1/7SK, flavopiridol-sensitivity, and in vivo KD

    PMID:24434558

    Open questions at the time
    • How hnRNPL selects elongation-dependent target genes unclear
    • Direct versus 7SK-bridged interactions not fully dissected
  6. 2016 High

    Defined a structural role for HNRNPL as an architectural adaptor bridging two RNase-sensitive substructures of the Sam68 nuclear body.

    Evidence Fluorescent cDNA screen of 32,651 clones, RNase treatment, systematic siRNA KD, and confocal imaging

    PMID:27377249

    Open questions at the time
    • Identity of the architectural RNAs bound by each RRM set not determined
    • Function of the SNB itself remains unclear
  7. 2013 High

    First lncRNA-templated transcriptional role: THRIL recruits hnRNPL to the TNFα promoter, establishing the recurring paradigm of ncRNA-guided HNRNPL chromatin recruitment.

    Evidence Reciprocal RIP, RNA pulldown, ChIP, and lentiviral KD with transcriptome analysis in macrophages

    PMID:24371310

    Open questions at the time
    • Whether HNRNPL activates or represses depends on context not generalized here
    • Mechanism of Pol II engagement at the promoter not resolved
  8. 2017 Medium

    Defined a pro-survival, oncogenic function in tumor cells through stabilization/binding of p53 and BCL-2 transcripts and sustained MAPK signaling.

    Evidence RIP, co-IP, siRNA/overexpression, and xenograft models in bladder and prostate cancer cells

    PMID:28038443 PMID:28088793

    Open questions at the time
    • Direct versus indirect effects on p21/cyclin levels not separated
    • RNA binding elements within targets not mapped
  9. 2019 High

    Generalized HNRNPL as an enhancer-RNA-associated co-activator: seRNA-1 recruits it to drive Pol II and H3K36me3 deposition during myogenesis, with transcriptome-wide eRNA association.

    Evidence RIP, ChIRP, ChIP for Pol II/H3K36me3, and in vivo loss-of-function during myogenic differentiation

    PMID:31857580

    Open questions at the time
    • How eRNA binding mechanistically stabilizes Pol II not defined
    • Selectivity of HNRNPL for specific enhancers unexplained
  10. 2019 High

    Demonstrated HNRNPL chromatin co-activator function is required for tissue homeostasis: it binds integrin/ECM gene loci, recruits Pol II, and maintains epidermal stem cells.

    Evidence ChIP, ChIP-seq, siRNA KD in keratinocytes, and conditional KO mouse epidermis with RNA-seq

    PMID:34543262

    Open questions at the time
    • Whether recruitment is RNA-dependent at these loci not tested
    • Distinction from splicing-based contributions to phenotype incomplete
  11. 2019 High

    Established post-translational control of HNRNPL abundance via FBXO16-SCF ubiquitination targeting its RRM3 domain.

    Evidence Co-IP, in vitro ubiquitination assay, domain mapping, KO/rescue, and xenograft model

    PMID:34333526

    Open questions at the time
    • Signals triggering FBXO16-mediated degradation not identified
    • Functional consequences for splicing/transcription targets not surveyed
  12. 2020 High

    Defined the cytoplasmic mRNA-stabilizing mechanism: HNRNPL binds CA-repeat coding-region elements to protect MTNR1A from EXOSC10-mediated decay.

    Evidence RNAi screen, RIP, mRNA stability assay, and KD/OE with downstream cAMP-CREB readout

    PMID:32730662

    Open questions at the time
    • How HNRNPL antagonizes the exosome mechanistically not resolved
    • Breadth of CA-repeat target transcriptome not mapped here
  13. 2021 Medium

    Showed lncRNAs can both stabilize HNRNPL protein (CASC8 blocking polyubiquitination) and act as decoys to sequester it from mRNA targets (SNHG1, SNHG6), tuning its functional output.

    Evidence RNA pulldown, RIP, ubiquitination/co-IP assays, and rescue experiments in cancer models

    PMID:33542227 PMID:34252487 PMID:35982900

    Open questions at the time
    • Competition stoichiometry between decoy lncRNAs and mRNA targets not quantified
    • Single-lab studies per lncRNA
  14. 2024 High

    Demonstrated splicing-program control underlies HNRNPL essentiality in B cell activation, regulating histone modifiers (KDM6A, SIRT1) and shaping global histone marks and mitochondrial function.

    Evidence Conditional KO mice, comparative RNA-seq across 8+ cell types, and H3K27me3/H3K9ac ChIP

    PMID:38744970

    Open questions at the time
    • Direct splicing targets versus downstream chromatin effects not fully separated
    • Mechanism linking splicing changes to ROS not resolved
  15. 2024 Medium

    Extended cytoplasmic mRNA stabilization to metabolic and immune outputs by stabilizing S100A9, WSB1, and CCL5 transcripts.

    Evidence RIP, RNA pulldown, actinomycin D decay assays, and rescue/xenograft models

    PMID:36869127 PMID:38368714 PMID:38822203

    Open questions at the time
    • Whether all targets share the CA-repeat recognition mode not confirmed
    • circMGA positive-feedback mechanism mechanistically incomplete
  16. 2023 Medium

    Identified an NMD-protective function: HNRNPL (with PTBP1) shields CFTR mRNA bearing nonsense alleles from decay.

    Evidence siRNA depletion and overexpression with quantitative mRNA decay measurement in 16HBE14o- cells across G542X/W1282X contexts

    PMID:38045134

    Open questions at the time
    • Binding site on CFTR mRNA not mapped
    • Mechanism of NMD antagonism not defined
  17. 2025 High

    Established that HNRNPL forms chromatin phase-separated condensates that activate transcription, templated by a promoter-derived non-coding RNA at PIK3CB.

    Evidence ChIP, phase-separation assays, RIP, and CDX/PDO models with glycolysis measurement

    PMID:40413189

    Open questions at the time
    • Domains driving condensation not mapped
    • Generality of condensate-driven activation across loci not established
  18. 2025 High

    Connected HNRNPL splicing activity to in vivo myelination via NMD-controlled levels and Mag/Nfasc splicing in oligodendrocytes.

    Evidence Conditional Smg5 KO in oligodendrocyte lineage, RNA-seq, splicing assays, EM of myelin, and motor testing

    PMID:40930975

    Open questions at the time
    • Direct splicing mechanism on Mag/Nfasc introns not biochemically detailed
    • HNRNPL auto-regulation through NMD not fully traced
  19. 2025 Medium

    Added a chromatin/DNA-repair role: an HNRNPL/CstF64-eRNA complex at the IgH 3'RR promotes Pol II elongation and NHEJ-mediated repair to govern class switch and locus suicide recombination.

    Evidence Co-IP, ChIP, eRNA transcription assays, CSR/LSR reporters, NHEJ assay, and 53BP1/Ku80 recruitment

    PMID:40902003

    Open questions at the time
    • How HNRNPL facilitates 53BP1/Ku80 recruitment mechanistically unclear
    • Direct versus eRNA-mediated contributions not separated
  20. 2025 Medium

    Identified SENP3-mediated deSUMOylation as a second post-translational route controlling HNRNPL stability and a downstream Neat1-caspase-1 pyroptosis axis in liver injury.

    Evidence Co-IP, SUMOylation assay, and hepatocyte-specific SENP3 KO mice with Neat1/caspase-1 readout

    PMID:40792025

    Open questions at the time
    • SUMO acceptor sites on HNRNPL not mapped
    • Link between SUMO status and Neat1 regulation not mechanistically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HNRNPL's distinct activities—CA-rich splicing, cytoplasmic mRNA stabilization, ncRNA-guided chromatin co-activation, and condensate formation—are coordinated and selected within a given cell remains unresolved.
  • No unified model linking RRM usage to functional partitioning
  • Domain determinants of phase separation versus RNA binding undefined
  • Rules governing which ncRNA recruits versus sequesters HNRNPL unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0140098 catalytic activity, acting on RNA 4 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2 GO:0140313 molecular sequestering activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 5 GO:0000228 nuclear chromosome 3 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2
Partners
APE1CCNT2CDK9CSTF64FBXO16HEXIM1PTBP1SENP3
Complex memberships
FBXO16-SCF E3 ligase complexP-TEFb / 7SK snRNP-associated complexSam68 nuclear bodyhnRNPL/CstF64 eRNA complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 hnRNPL binds to the lncRNA THRIL (linc1992) and the THRIL-hnRNPL complex regulates transcription of the TNFα gene by binding to its promoter in THP1 macrophages. RNA immunoprecipitation, RNA pulldown, ChIP, lentiviral knockdown with transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America High 24371310
2002 hnRNP-L and APE1 form a protein complex that binds the nCaRE-B2 repressor element in the APE1 promoter, and the APE1–hnRNP-L protein–protein interaction does not require the nCaRE-B2 DNA element, identifying a novel transcriptional regulatory role for hnRNP-L. Electrophoretic mobility shift assay, UV cross-linking, co-immunoprecipitation, pulldown assays Nucleic acids research Medium 11809897
2012 hnRNPL binds LINE-1 ORF2 IRES RNA (confirmed by RNA affinity chromatography) and functions as a negative regulator of L1 retrotransposition; hnRNPL knockdown dramatically increased L1 retrotransposition as well as L1 RNA and ORF1 protein levels. RNA affinity chromatography, siRNA knockdown, L1 retrotransposition reporter assay Nucleic acids research High 23161687
2014 hnRNPL interacts with P-TEFb components CDK9, CCNT2, HEXIM1, and the 7SK RNA; hnRNPL knockdown reduces transcripts sensitive to the P-TEFb inhibitor flavopiridol and disrupts the association of 7SK RNA with Aire-containing complexes, indicating hnRNPL promotes RNA polymerase II elongation by facilitating delivery of inactive P-TEFb to Aire. Genome-scale shRNA screen, co-immunoprecipitation with P-TEFb components, flavopiridol-sensitivity assay, lentiviral KD mice Proceedings of the National Academy of Sciences of the United States of America High 24434558
2016 HNRNPL acts as a structural adaptor in the Sam68 nuclear body (SNB), joining two distinct RNase-sensitive substructures (the DBC1 body substructure and the Sam68 substructure) through interactions of two sets of RNA recognition motifs (RRMs) with putative architectural RNAs in each substructure. Fluorescent cDNA screen of 32,651 clones for RNase-sensitive nuclear foci, RNase treatment, siRNA knockdown of each SNB protein, confocal microscopy The Journal of cell biology High 27377249
2019 The seRNA-1 enhancer RNA interacts with hnRNPL via a CAAA tract; disrupting seRNA-1-hnRNPL interaction reduces RNA Pol II and H3K36me3 deposition at the myoglobin (Mb) locus and attenuates its transcription during myogenic differentiation. Transcriptome-wide analysis shows hnRNPL association with eRNAs is a general phenomenon. RNA immunoprecipitation, ChIRP, ChIP for Pol II and H3K36me3, in vitro and in vivo loss-of-function Nature communications High 31857580
2009 hnRNP-L binds the right terminal stem-loop domain of HDV genomic RNA in vitro and co-immunoprecipitates with both polarities of HDV RNA within HeLa cells, indicating it is a host factor that associates with the HDV replication complex. UV cross-linking/mass spectrometry, RNA affinity chromatography, co-immunoprecipitation in HeLa cells Virology Medium 19464723
2017 hnRNP-L knockdown in bladder cancer cells results in G1-phase cell cycle arrest, enhanced apoptosis, decreased Bcl-2, increased caspase-3/-6/-9, and inhibition of MAPK signaling, establishing hnRNP-L as a pro-survival factor that sustains MAPK signaling and suppresses intrinsic apoptosis. siRNA knockdown, cell cycle analysis, apoptosis assay, xenograft tumor model, western blotting Oncotarget Medium 28088793
2017 HnRNP-L promotes prostate cancer cell proliferation by binding p53 mRNA (confirmed by RIP) affecting p21/cyclin levels, and promotes anti-apoptosis by directly binding BCL-2. RNA immunoprecipitation (RIP), co-immunoprecipitation, siRNA/overexpression, xenograft model Oncotarget Medium 28038443
2019 FBXO16, an F-box E3 ubiquitin ligase, assembles an SCF complex that directly ubiquitinates hnRNPL for proteasomal degradation by binding to the RRM3 domain of hnRNPL via FBXO16's C-terminal region. Co-immunoprecipitation, ubiquitination assay, domain-mapping, siRNA/KO, xenograft model Cell death & disease High 34333526
2021 HNRNPL promotes the stability of hnRNPL protein by protecting it from polyubiquitination and proteasomal degradation when the lncRNA CASC8 binds to it; CASC8-hnRNPL interaction inhibits hnRNPL polyubiquitination. Co-immunoprecipitation, ubiquitination assay, RNA pulldown, siRNA knockdown, xenograft model International journal of biological sciences Medium 35982900
2021 HNRNPL binds to the lncRNA SNHG1 and this interaction impairs HNRNPL's ability to promote E-cadherin (CDH1) mRNA translation, thereby activating EMT in prostate cancer cells. RNA pulldown, RIP, RNA-seq, immunoblotting, rescue experiments Cell death & disease Medium 33542227
2021 HNRNPL binds the lncRNA SNHG6 and normally stabilizes SETD7 mRNA; when SNHG6 acts as a decoy to sequester HNRNPL, SETD7 mRNA stability is reduced, promoting HCC progression. Quantitative proteomics, RNA pulldown, RIP, siRNA knockdown, rescue experiments Cancer letters Medium 34252487
2020 Cytoplasmic hnRNPL stabilizes MTNR1A mRNA through CA-repeat elements in its coding region, protecting the transcript from degradation by exosome component 10 (EXOSC10); hnRNPL knockdown or overexpression correspondingly decreases or increases MTNR1A RNA and downstream cAMP-CREB signaling. RNA interference screen, hnRNPL knockdown/overexpression, mRNA stability assay, RIP, western blotting Journal of cellular physiology High 32730662
2020 Protein kinase C theta (PKCθ) signaling modulates hnRNPL activity in induced regulatory T cells; loss of PKCθ function alters hnRNPL-dependent post-transcriptional regulation, which in turn controls PCMT1 expression and FOXP3 stability. Cell-penetrating peptide mimic delivery, RNA processing analysis, knockdown/overexpression, flow cytometry Molecular therapy : the journal of the American Society of Gene Therapy Low 32592691
2019 hnRNPL binds chromatin at integrin and extracellular matrix genes in epidermal stem cells, recruits RNA polymerase II to these loci, and stabilizes Pol II transcription through these genes; HNRNPL loss causes premature differentiation and detachment of the basal epidermal layer due to diminished integrin/ECM expression. ChIP, ChIP-seq, siRNA knockdown in primary human keratinocytes, in vivo mouse epidermis KO, RNA-seq PLoS biology High 34543262
2012 hnRNPL knockdown in spermatogenic cells leads to inhibited proliferation and increased apoptosis, whereas knockdown in Sertoli cells decreases apoptosis; hnRNPL regulates CEACAM1 in GC-1 spermatogenic cells and iNOS in TM4 Sertoli cells, establishing hnRNPL as a key regulator of spermatogenesis. 2D-gel proteomics, MALDI-TOF MS, siRNA knockdown in vitro and in vivo, immunohistochemistry, western blotting Journal of proteomics Medium 22245417
2019 hnRNPL directly targets p53 mRNA (confirmed by RIP) in Wilms tumor cells; knockdown of hnRNPL inhibits expression of both p53 and Bcl-2, reduces proliferation, and promotes apoptosis in vitro and suppresses xenograft growth in vivo. RIP, siRNA knockdown, MTT assay, flow cytometry, RT-qPCR, western blot, xenograft model OncoTargets and therapy Medium 31213844
2019 hnRNPL inhibits osteogenic differentiation of periodontal ligament stem cells by down-regulating the H3K36me3 methyltransferase SETD2; the AKT pathway governs hnRNPL levels in response to Sr ions. Knockdown/overexpression, western blotting, osteogenic differentiation assay, AKT pathway inhibitor Journal of cellular and molecular medicine Low 30746871
2019 HNRNPL binds the 3′UTR of BUB1 mRNA at the polymorphic marker D2S1888 and blocks miR-155 targeting of BUB1, thereby restoring BUB1 protein expression and stabilizing karyotypes in chronic lymphocytic leukemia-derived transformed cells. RNA binding assay, expression analysis of BUB1 vs miR-155, knockdown/rescue experiments Cancers Low 31018621
2022 lncFAM71E1-2:2 (lncFAM) recruits HNRNPL to the MYBPC2 promoter, increasing MYBPC2 mRNA transcription and production of the myogenic protein MYBPC2 to promote human myoblast differentiation into myotubes. ChIRP-MS, ChIRP, siRNA knockdown/overexpression, myotube differentiation assay, qPCR Nucleic acids research Medium 36533518
2024 hnRNPL is essential for B cell activation, germinal center formation, and antibody responses; it regulates alternative splicing of histone modifiers KDM6A and SIRT1 (conserved across ≥8 cell types), and its loss causes global changes in H3K27me3 and H3K9ac, dysfunctional mitochondria, and ROS overproduction in mouse B cells. Conditional KO mice, RNA-seq (comparative across 8+ cell types), H3K27me3/H3K9ac ChIP, flow cytometry, proliferation/apoptosis assays EMBO reports High 38744970
2025 hnRNPL forms phase-separated condensates on chromatin that activate PIK3CB transcription and glycolysis in ovarian cancer cells; a non-coding RNA transcribed from the PIK3CB promoter interacts with hnRNPL and promotes its condensation. ChIP, phase-separation assays, RNA immunoprecipitation, CDX and PDO models, hnRNPL KD/OE, glycolysis measurement Nature communications High 40413189
2023 HNRNPL stabilizes circMGA RNA, and the circMGA/HNRNPL complex stabilizes CCL5 mRNA, promoting CCL5 secretion and CD8+ T cell chemoattraction in bladder cancer; in turn, HNRNPL increases circMGA stability, forming a positive feedback loop. RIP, RNA pulldown, siRNA knockdown, luciferase assay, mouse xenograft with immune reconstitution Oncogene Medium 36869127
2023 HNRNPL and PTBP1 protect CFTR mRNA from nonsense-mediated decay (NMD); depletion of HNRNPL specifically reduces CFTR mRNA abundance (increases mRNA decay) in cells bearing G542X or W1282X nonsense alleles, while HNRNPL overexpression increases CFTR mRNA levels most prominently in these nonsense-allele lines. siRNA depletion, exogenous overexpression, quantitative PCR for mRNA abundance and decay rate in 16HBE14o- cells Heliyon Medium 38045134
2025 hnRNPL promotes exon 13 skipping in SLK pre-mRNA by recognizing introns 12 and 13, generating the oncogenic SLK-S isoform that activates ERK signaling and enhances HCC cell invasion and metastasis. RNA pulldown, RIP, alternative splicing assays, siRNA knockdown/overexpression, invasion/metastasis assays, in vivo mouse model Biochemical pharmacology Medium 41046074
2025 hnRNPL forms a complex with CstF64 (a polyadenylation factor) associated with enhancer RNAs (eRNAs) at the IgH 3′ regulatory region; this hnRNPL/CstF64 complex promotes RNA polymerase II elongation and eRNA transcription at the 3′RR, and also promotes NHEJ-mediated DNA repair by facilitating 53BP1 and Ku80 recruitment, thereby regulating class switch recombination (CSR) and locus suicide recombination (LSR). Co-immunoprecipitation, ChIP, eRNA transcription assay, CSR/LSR reporter assays, NHEJ assay, 53BP1/Ku80 recruitment assay Nucleic acids research Medium 40902003
2025 SMG5-mediated NMD degrades PTC-containing Hnrnpl variant transcripts in oligodendrocyte lineage cells; loss of SMG5 increases these aberrant Hnrnpl variants and impairs oligodendrocyte differentiation; HNRNPL promotes alternative splicing of myelin-associated genes Mag and Nfasc to support oligodendrocyte differentiation. Conditional Smg5 KO in oligodendrocyte lineage, RNA-seq, myelin gene expression analysis, splicing assay, electron microscopy of myelin sheaths, motor function testing The Journal of neuroscience High 40930975
2023 KIT D816V mutation (but not wild-type KIT) specifically induces phosphorylation of HNRNPL and HNRNPK in COS-1 cells, without requiring the ligand SCF; wild-type KIT and HNRNPL have different subcellular distributions (nuclear for HNRNPL, cytosol/membrane for wild-type KIT), whereas KIT D816V is predominantly cytosolic. Immunoprecipitation, western blot, confocal microscopy, transfection of WT vs D816V KIT with HNRNPL Xi bao yu fen zi mian yi xue za zhi Low 36872432
2025 SENP3 interacts with HNRNPL and facilitates its deSUMOylation and proteasomal degradation in hepatocytes during acute liver injury; this reduction in HNRNPL decreases Neat1 lncRNA levels, impairing caspase-1 activation and pyroptosis. Co-immunoprecipitation, SUMOylation assay, SENP3 KO mice (hepatocyte-specific), Neat1/caspase-1 assay, western blotting iScience Medium 40792025
2024 HNRNPL promotes S100A9 mRNA stability through direct RNA binding (confirmed by RIP and RNA pulldown), thereby sustaining ferroptosis in hepatocellular carcinoma cells by maintaining iron and ROS levels. RIP, RNA pulldown, actinomycin D mRNA stability assay, sh-HNRNPL and oe-S100A9 rescue, in vivo xenograft Translational oncology Medium 38368714
2018 lncITPF binds hnRNP-L (confirmed by RNA pulldown, LC-MS, and RIP) and, through hnRNP-L, regulates H3 and H4 histone acetylation at the ITGBL1 promoter to promote pulmonary fibrosis. RNA pulldown, LC-MS, RIP, ChIP-qPCR, CRISPR-Cas9, siRNA knockdown Molecular therapy : the journal of the American Society of Gene Therapy Medium 30528088
2024 hnRNPL regulates alternative splicing of tropomyosin in cardiac muscle cells (confirmed in C2C12 myoblasts); hnRNPL protein increases in failing hearts from mice with transaortic constriction-induced HF and from HF patients, and knockdown of the Drosophila ortholog Smooth induces cardiomyopathy. Computational binding site prediction, RT-PCR splicing assay in C2C12 myoblasts, Drosophila smooth KD, western blot from human/mouse heart tissue FEBS letters Medium 39300280
2025 CircROR1 recruits HNRNPL to the nucleus and influences its nuclear translocation; the circROR1/HNRNPL complex prevents intron retention in FOXO4 mRNA, promoting FOXO4ζ isoform over FOXO4α and enhancing melanoma metastasis. RNA pulldown-MS, RIP, nuclear/cytoplasmic fractionation, FISH, RNA-seq, overexpression/KD, xenograft model Molecular cancer Medium 41530849
2024 hnRNPL increases WSB1 mRNA stability by directly binding WSB1 mRNA (confirmed by RIP and RNA pulldown), thereby promoting lipid droplet accumulation and proliferation in clear cell renal cell carcinoma cells. RIP, RNA pulldown, actinomycin D mRNA stability assay, CCK-8, Oil Red O/BODIPY staining, siRNA knockdown Cell biochemistry and biophysics Low 38822203

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proceedings of the National Academy of Sciences of the United States of America 510 24371310
2021 HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 108 34258149
2023 HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway. Journal of experimental & clinical cancer research : CR 82 36747239
2002 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter. Nucleic acids research 76 11809897
2012 hnRNPL and nucleolin bind LINE-1 RNA and function as host factors to modulate retrotransposition. Nucleic acids research 75 23161687
2019 MyoD induced enhancer RNA interacts with hnRNPL to activate target gene transcription during myogenic differentiation. Nature communications 73 31857580
2020 A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3. Molecular cancer 66 32669100
2019 Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling. Clinical cancer research : an official journal of the American Association for Cancer Research 60 31492748
2014 An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proceedings of the National Academy of Sciences of the United States of America 55 24434558
2022 The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. International journal of biological sciences 53 35982900
2016 The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL. The Journal of cell biology 53 27377249
2018 lncITPF Promotes Pulmonary Fibrosis by Targeting hnRNP-L Depending on Its Host Gene ITGBL1. Molecular therapy : the journal of the American Society of Gene Therapy 49 30528088
2022 hnRNPL-activated circANKRD42 back-splicing and circANKRD42-mediated crosstalk of mechanical stiffness and biochemical signal in lung fibrosis. Molecular therapy : the journal of the American Society of Gene Therapy 42 35278674
2021 LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer. Cell death & disease 40 33542227
2012 HnRNPL as a key factor in spermatogenesis: Lesson from functional proteomic studies of azoospermia patients with sertoli cell only syndrome. Journal of proteomics 40 22245417
2009 The hepatitis delta virus RNA genome interacts with eEF1A1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2. Virology 40 19464723
2020 Heterogeneous nuclear ribonucleoprotein (hnRNPL) in cancer. Clinica chimica acta; international journal of clinical chemistry 36 32376323
2017 HnRNP-L mediates bladder cancer progression by inhibiting apoptotic signaling and enhancing MAPK signaling pathways. Oncotarget 34 28088793
2021 FBXO16-mediated hnRNPL ubiquitination and degradation plays a tumor suppressor role in ovarian cancer. Cell death & disease 30 34333526
2017 HnRNP-L promotes prostate cancer progression by enhancing cell cycling and inhibiting apoptosis. Oncotarget 30 28038443
2021 lncRNA SNHG6 promotes hepatocellular carcinoma progression by interacting with HNRNPL/PTBP1 to facilitate SETD7/LZTFL1 mRNA destabilization. Cancer letters 28 34252487
2017 Smooth, an hnRNP-L Homolog, Might Decrease Mitochondrial Metabolism by Post-Transcriptional Regulation of Isocitrate Dehydrogenase (Idh) and Other Metabolic Genes in the Sub-Acute Phase of Traumatic Brain Injury. Frontiers in genetics 26 29187863
2020 Long noncoding RNA LEF1-AS1 binds with HNRNPL to boost the proliferation, migration, and invasion in osteosarcoma by enhancing the mRNA stability of LEF1. Journal of cellular biochemistry 25 31930565
2023 Regulation of CD8+ T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer. Oncogene 24 36869127
2016 Long noncoding RNA uc.345 promotes tumorigenesis of pancreatic cancer by upregulation of hnRNPL expression. Oncotarget 22 27689400
2020 Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1. Human molecular genetics 18 32037441
2019 HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2. Journal of cellular and molecular medicine 18 30746871
2023 Circular RNA CircPDS5B impairs angiogenesis following ischemic stroke through its interaction with hnRNPL to inactivate VEGF-A. Neurobiology of disease 17 36925052
2024 Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation. EMBO reports 16 38744970
2025 ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 40091520
2022 Enhanced myogenesis through lncFAM-mediated recruitment of HNRNPL to the MYBPC2 promoter. Nucleic acids research 15 36533518
2019 HnRNPL promotes Wilms tumor progression by regulating the p53 and Bcl2 pathways. OncoTargets and therapy 15 31213844
2010 NSP 5a3a's link to nuclear-cyto proteins B23 and hnRNP-L between normal and aberrant breast cell lines. Cell cycle (Georgetown, Tex.) 14 20237420
2021 Regulation of integrin and extracellular matrix genes by HNRNPL is necessary for epidermal renewal. PLoS biology 13 34543262
2020 Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells. Molecular therapy : the journal of the American Society of Gene Therapy 13 32592691
2022 LINC01588 regulates WWP2-mediated cardiomyocyte injury by interacting with HNRNPL. Environmental toxicology 11 35258167
2019 HNRNPL Restrains miR-155 Targeting of BUB1 to Stabilize Aberrant Karyotypes of Transformed Cells in Chronic Lymphocytic Leukemia. Cancers 11 31018621
2020 HNRNPL affects the proliferation and apoptosis of colorectal cancer cells by regulating PD-L1. Pathology, research and practice 10 33418347
2020 The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells. Journal of cellular physiology 8 32730662
2024 HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression. Translational oncology 7 38368714
2018 Expression of TNF- and HNRNPL-related Immunoregulatory Long Non-coding RNA (THRIL) in Acute Myeloid Leukemia: Is There Any Correlation? Iranian journal of allergy, asthma, and immunology 7 29908545
2003 PLG regulates hnRNP-L expression in the rat striatum and pre-frontal cortex: identification by ddPCR. Peptides 7 12576095
2022 Long non-coding RNA lincRNA-erythroid prosurvival (EPS) alleviates cerebral ischemia/reperfusion injury by maintaining high-temperature requirement protein A1 (Htra1) stability through recruiting heterogeneous nuclear ribonucleoprotein L (HNRNPL). Bioengineered 5 35549989
2025 hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer. Nature communications 4 40413189
2023 RNA binding proteins PTBP1 and HNRNPL regulate CFTR mRNA decay. Heliyon 4 38045134
2025 Exon 13 skipping mediated by HNRNPL facilitates truncated SLK-induced metastasis in hepatocellular carcinoma. Biochemical pharmacology 3 41046074
2023 hnRNPL expression dynamics in the embryo and placenta. Gene expression patterns : GEP 3 37148985
2025 Smg5 Enhances Oligodendrocyte Differentiation via Nonsense-Mediated mRNA Decay of Hnrnpl Variant Transcripts. The Journal of neuroscience : the official journal of the Society for Neuroscience 2 40930975
2025 hnRNPL-CstF64 complex: coordinating CSR and LSR in IgH locus recombination dynamics through eRNA and NHEJ regulation. Nucleic acids research 1 40902003
2024 The splicing factor hnRNPL demonstrates conserved myocardial regulation across species and is altered in heart failure. FEBS letters 1 39300280
2023 [D816V mutation of KIT specifically induces phosphorylation of HNRNPL and HNRNPK in COS-1 cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 36872432
2026 CircROR1 binds HNRNPL to regulate FOXO4 pre-mRNA splicing, promoting cutaneous melanoma metastasis and serving as a therapeutic target via RNAi-loaded PEG-LNPs. Molecular cancer 0 41530849
2026 LINC01012 Drives Hepatitis B-Related Hepatocellular Carcinoma Progression Through HNRNPL-Mediated Stabilization of Serine/Threonine-Protein Kinase-S. Journal of medical virology 0 42080810
2025 CircCDYL Association With hnRNPL Modulates CDYL Isoform Switching in Breast Cancer Cells. Cancer science 0 40702809
2025 SENP3 protects hepatocyte from pyroptosis during acute liver injury through deSUMOylation of HNRNPL. iScience 0 40792025
2025 The impact of Hnrnpl deficiency on transcriptional patterns of developing muscle cells. FEBS open bio 0 40944391
2024 HNRNPL Increases WSB1 mRNA Stability to Promote Proliferation and Lipid Droplets in Clear Cell Renal Cell Carcinoma. Cell biochemistry and biophysics 0 38822203

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