Affinage

RBM10

RNA-binding protein 10 · UniProt P98175

Length
930 aa
Mass
103.5 kDa
Annotated
2026-04-28
83 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM10 is a nuclear RNA-binding protein that functions as a master splicing regulator promoting exon skipping across hundreds of pre-mRNAs, with additional splicing-independent roles in 3'-end RNA processing, DNA replication fork stability, and chromatin organization. Its RRM1-ZnF-RRM2 domains cooperatively bind exonic GGA-centered motifs and intronic C-rich sequences with nanomolar affinity to direct exon skipping of targets including NUMB, Bcl-x, Fas, TERT, and cytoskeletal/ECM transcripts (VCL, TNC, CD44), and it functions as a constitutive U2 snRNP component at intronic branch sites where its conserved zinc finger peptide is required for spliceosomal integration and exon repression (PMID:28379442, PMID:38537639, PMID:39992626). Beyond splicing, RBM10 associates with the poly(A) polymerase Star-PAP via RRM2 to direct 3'-end processing of anti-hypertrophy cardiac mRNAs under control of cSrc-mediated tyrosine phosphorylation, and interacts with active replication forks via PRIM1 to recruit HDAC1 for H4K16 deacetylation and R-loop resolution (PMID:30257214, PMID:38309577, PMID:39080280). RBM10 loss generates aberrant exon-inclusion isoforms that activate RAC1 and drive metastasis, while dengue NS5 and HIV-1 Vpu exploit proteasome-mediated RBM10 degradation to overcome its antiviral splicing and innate immune functions including RIG-I ubiquitination (PMID:39992626, PMID:32432721, PMID:40742131).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2013 High

    PAR-CLIP mapping established that RBM10 directly binds pre-mRNAs near splice sites transcriptome-wide and functions as a general exon-skipping regulator, resolving its role beyond candidate gene studies.

    Evidence PAR-CLIP, loss/gain-of-function, and minigene assays in human cells

    PMID:24000153

    Open questions at the time
    • Binding motif specificity of individual RNA-binding domains not yet resolved
    • Mechanism of exon skipping (steric, spliceosome recruitment, or other) unknown
  2. 2013 Medium

    Systematic mutagenesis identified three cooperating nuclear localization sequences including the OCRE domain as a novel NLS, explaining how RBM10 achieves robust nuclear accumulation.

    Evidence Deletion/substitution mutagenesis with EGFP/FLAG-fusion localization in cultured cells

    PMID:23294349

    Open questions at the time
    • Whether nuclear import is regulated by post-translational modification was not tested
    • No importin interaction partners identified
  3. 2014 Medium

    RBM10 was shown to regulate alternative splicing of specific apoptosis regulators Fas and Bcl-x, linking its exon-skipping activity to apoptotic signaling outcomes.

    Evidence Splicing assays and binding site analysis with knockdown/overexpression

    PMID:24530524

    Open questions at the time
    • Bcl-x splice regulation not yet connected to in vivo phenotype
    • Binding site consensus not structurally validated
  4. 2015 High

    NMR determination of the OCRE domain structure revealed a distinctive six-β-strand globular fold with tyrosine triplets, establishing it as a conserved protein-protein interaction module for spliceosomal contacts.

    Evidence NMR structure determination

    PMID:26712279

    Open questions at the time
    • Specific spliceosomal binding partners of OCRE not identified
    • Functional consequence of OCRE mutations on splicing regulation not tested
  5. 2016 High

    The RNA recognition code of RBM10 was deciphered: RRM1-ZnF recognizes exonic GGA motifs while RRM2 recognizes intronic C-rich sequences, explaining how dual binding units achieve target specificity for NUMB exon 9 and other regulated exons.

    Evidence RNA binding assays, structural modeling, mutagenesis, and splicing reporters

    PMID:26853560 PMID:28379442

    Open questions at the time
    • How the oncogenic V354E mutation disrupts splicing without affecting RNA binding remained mechanistically unexplained
    • No high-resolution co-crystal structure of RBM10-RNA complex
  6. 2016 High

    iCLIP in mouse embryonic cells confirmed predominant intronic binding in vivo and demonstrated that RBM10 knockout causes proliferation defects and altered differentiation in embryonic stem cells, establishing developmental relevance.

    Evidence iCLIP, RNA-seq, RBM10 KO mouse cells

    PMID:27763814

    Open questions at the time
    • Which specific splicing changes drive the differentiation phenotype not resolved
    • In vivo developmental phenotype in whole organism not reported
  7. 2016 Medium

    Discovery of a cytoplasmic, splicing-independent role for RBM10: Fyn kinase induces RBM10 translocation to the cell periphery where it promotes FilGAP localization and Rac suppression, revealing a non-nuclear function.

    Evidence Co-IP, fluorescence microscopy, siRNA knockdown, cell spreading assays

    PMID:26751795

    Open questions at the time
    • Direct phosphorylation of RBM10 by Fyn not demonstrated
    • Whether FilGAP interaction occurs through direct binding or RNA-mediated bridging unclear
    • Not independently replicated
  8. 2017 High

    NMR structures of individual RRM1, ZnF1, and RRM2 domains, combined with quantitative binding showing ~20 nM cooperative affinity of the RRM1-ZnF1-RRM2 polypeptide for Fas exon 6, defined the structural basis for high-affinity RNA recognition.

    Evidence NMR structure determination and in vitro RNA binding reconstitution with domain combinations

    PMID:29450990

    Open questions at the time
    • No structure of the full-length protein or multi-domain complex with RNA
    • OCRE domain contribution to RNA binding not addressed
  9. 2017 High

    RBM10 was found to autoregulate its own expression and cross-regulate paralog RBM5 via AS-NMD of specific exons, establishing a homeostatic feedback circuit between the two paralogs.

    Evidence Computational analysis plus experimental validation of AS-NMD events

    PMID:28586478

    Open questions at the time
    • Whether RBM5 reciprocally cross-regulates RBM10 via the same mechanism remained unclear until later RIP-Seq data
    • Physiological consequence of disrupting the autoregulatory loop not tested in vivo
  10. 2017 Medium

    RBM10 was shown to control Dnmt3b isoform splicing, linking its splicing activity to DNA methylation regulation at NF-κB-responsive promoters and inflammatory gene suppression.

    Evidence Mouse models, splicing assays, promoter methylation analysis, NF-κB reporter assays

    PMID:29309623

    Open questions at the time
    • Whether RBM10 directly binds Dnmt3b pre-mRNA not confirmed by CLIP
    • Relative contribution to inflammation versus other methylation-dependent pathways unclear
  11. 2018 High

    A splicing-independent function was discovered: RBM10 binds the Star-PAP catalytic domain via RRM2 and directs 3'-end polyadenylation of anti-hypertrophy mRNAs, establishing RBM10 as a specificity factor for non-canonical polyadenylation.

    Evidence Reciprocal Co-IP, domain mapping, functional knockdown/overexpression in cardiomyoblasts and rat hearts

    PMID:30257214

    Open questions at the time
    • Structural basis of RRM2–Star-PAP interaction not determined
    • Full repertoire of Star-PAP targets dependent on RBM10 not mapped
  12. 2020 High

    Dengue NS5 was found to target RBM10 for proteasomal degradation, and RBM10 was shown to promote RIG-I ubiquitination for innate immune signaling, establishing RBM10 as an antiviral host factor exploited by viral immune evasion.

    Evidence Co-IP, RNA-seq, proteasome inhibitor rescue, RIG-I ubiquitination assays, overexpression/knockdown

    PMID:32432721

    Open questions at the time
    • Whether RBM10's antiviral effect operates through splicing, RIG-I activation, or both pathways was not fully dissected
    • Ubiquitin ligase mediating RBM10 degradation not identified
  13. 2020 Medium

    Overexpressed RBM10 was found to trap PLK4-STIL in the nucleus, depleting centrosomal pools and blocking centriole duplication, revealing a splicing-independent role in centrosome biology.

    Evidence KO cell lines with inducible re-expression, immunofluorescence, NES-forced cytoplasmic mutant

    PMID:31820547

    Open questions at the time
    • Whether endogenous RBM10 levels regulate centriole duplication physiologically unknown
    • Mechanism of PLK4-STIL nuclear sequestration not resolved
    • Only observed with overexpression, not at endogenous levels
  14. 2021 Medium

    HITS-CLIP confirmed global RBM10 occupancy on Star-PAP target mRNAs and showed that RBM10 knockdown abolishes Star-PAP recruitment, demonstrating that RBM10 is the essential RNA-targeting subunit of the Star-PAP complex.

    Evidence HITS-CLIP and RBM10 knockdown with Star-PAP binding measurements

    PMID:34576144

    Open questions at the time
    • Whether other RBPs can substitute for RBM10 in Star-PAP targeting not tested
    • Single laboratory observation
  15. 2021 Medium

    In fission yeast, the RBM10 ortholog was shown to associate with the Clr6 HDAC complex and to be required for heterochromatin assembly, establishing a conserved splicing-independent chromatin function.

    Evidence Proteomics, ChIP-seq, yeast genetics

    PMID:33468217

    Open questions at the time
    • Whether this HDAC-recruitment function is conserved in mammalian cells was not shown at this time
    • Mechanism of Rbm10–Clr6 interaction not defined
  16. 2021 Medium

    RBM10 nuclear body sequestration was mapped to two targeting sequences (KEKE motif and C2H2 ZnF), with NB accumulation inversely correlating with transcriptional activity, suggesting a storage/buffering mechanism for RBM10 splicing activity.

    Evidence Deletion mutagenesis, live-cell imaging, transcription inhibition

    PMID:34638866

    Open questions at the time
    • Whether NB sequestration quantitatively impacts splicing output not measured
    • Identity of NB scaffolding partners unknown
  17. 2021 Medium

    RBM10 was shown to regulate TERT splicing to produce a non-functional isoform, directly connecting its exon-skipping activity to telomerase suppression.

    Evidence RNA-IP, RNA pull-down, minigene assay, telomerase activity assay, xenograft models

    PMID:33520366

    Open questions at the time
    • Contribution of TERT splicing versus other targets to tumor suppression not dissected
    • Single cancer type tested
  18. 2022 High

    In EGFR-mutant lung cancer, RBM10 loss was shown to shift Bcl-x splicing toward anti-apoptotic Bcl-xL, conferring resistance to EGFR inhibitor-induced apoptosis, establishing clinical relevance of a specific splicing target.

    Evidence Patient-derived tumor models, genetic inactivation, splicing/apoptosis rescue

    PMID:35579943

    Open questions at the time
    • Whether Bcl-x is the sole mediator of EGFR inhibitor resistance or acts with other RBM10 targets not resolved
  19. 2024 High

    RBM10 was identified as a constitutive component of chromatin-associated U2 snRNP at branch sites, with a conserved zinc finger peptide required for spliceosomal integration, mechanistically explaining how RBM10 achieves exon repression from within the spliceosome.

    Evidence Chromatin-associated spliceosome isolation, proteomics, branch-site sequencing, deletion mutagenesis

    PMID:38537639

    Open questions at the time
    • Cryo-EM structure of RBM10-containing U2 snRNP complex not available
    • How RBM10 competes with or complements RBM5 within the same spliceosomal complex unclear
  20. 2024 Medium

    cSrc phosphorylation of RBM10 at Y81/Y500/Y971 was identified as a regulatory switch controlling nuclear localization and Star-PAP interaction during cardiac hypertrophy, establishing post-translational regulation of RBM10's non-splicing functions.

    Evidence In vitro kinase assays, phospho-deficient mutants, rat hypertrophy model, Co-IP

    PMID:38309577

    Open questions at the time
    • Whether cSrc phosphorylation also regulates RBM10 splicing activity not tested
    • Phosphatase that reverses these modifications unknown
  21. 2024 High

    A splicing-independent replication fork role was established: RBM10 interacts with PRIM1 at active forks, recruits HDAC1 for H4K16 deacetylation and R-loop resolution, and its loss creates a synthetic lethal dependency on WEE1, converging with the yeast Clr6/HDAC finding.

    Evidence CRISPR screen, replication fork assays, Co-IP, H4K16ac ChIP, R-loop analysis, WEE1 inhibitor treatment

    PMID:39080280

    Open questions at the time
    • Whether RBM10's replication fork function requires its RNA-binding activity or is purely protein-mediated unclear
    • Structural basis of PRIM1–RBM10 interaction not determined
  22. 2024 Medium

    RBM10 C761Y mutation in the C2H2 zinc finger was shown to disrupt interaction with SRSF2, preventing ASPM exon 18 skipping and activating Wnt/β-catenin signaling, identifying a specific splicing factor partnership mediating target exon regulation.

    Evidence Minigene reporter, Co-IP, RNA-seq, functional cancer assays in cholangiocarcinoma

    PMID:38576051

    Open questions at the time
    • Whether SRSF2 interaction is required for all RBM10-mediated exon skipping or target-specific unclear
    • Single cancer type studied
  23. 2025 High

    RBM10 loss was mechanistically connected to metastasis through specific exon-inclusion isoforms of VCL, TNC, and CD44 that activate RAC1, with isoform-specific knockdown rescuing metastatic phenotypes in vivo, demonstrating that aberrant splicing is the causal driver of RBM10-null metastatic competency.

    Evidence Transcriptomics, isoform-specific knockdown, RAC1-GTP pull-down, in vivo HrasG12V/Rbm10KO thyroid cancer model

    PMID:39992626

    Open questions at the time
    • Whether the VCL/TNC/CD44 splicing axis generalizes beyond thyroid cancer not tested
    • How these three isoforms cooperatively activate RAC1 at the biochemical level not resolved
  24. 2025 Medium

    HIV-1 Vpu was found to target RBM10 for proteasomal degradation analogous to dengue NS5, and RBM10 restricts HIV-1 by binding viral RNA and reducing incompletely spliced transcripts, establishing RBM10 as a broadly targeted antiviral factor.

    Evidence APEX2-proximity labeling/MS, IP-MS, proteasome inhibitor rescue, RNA binding assays

    PMID:40742131

    Open questions at the time
    • E3 ligase mediating Vpu-directed RBM10 degradation not identified
    • Whether RBM10 restricts other retroviruses unknown
  25. 2025 Medium

    RBM10 was shown to promote circRNA biogenesis by binding intronic flanking regions (preferentially 3') of circHIPK3 and circSMARCA5 and interacting with SF3B1, revealing position-dependent regulation of back-splicing.

    Evidence PAR-CLIP, RNA pulldown, splicing reporter, Co-IP with SF3B1, RNA-seq

    PMID:41673707

    Open questions at the time
    • Whether circRNA regulation contributes substantially to RBM10 tumor-suppressive function unknown
    • Global landscape of RBM10-dependent circRNAs not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: (1) the structural basis of RBM10 within the U2 snRNP complex, (2) how splicing and non-splicing functions are partitioned and regulated in different cell types, and (3) the full spectrum of post-translational modifications controlling RBM10 activity and localization.
  • No cryo-EM or crystal structure of RBM10 in a spliceosomal complex
  • Tissue-specific regulation of splicing versus replication fork versus polyadenylation functions not systematically addressed
  • Complete post-translational modification landscape not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0140098 catalytic activity, acting on RNA 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-69306 DNA Replication 1
Partners
FLNAHDAC1PRIM1RBM5SF3B1SRSF2TUT1YBX1
Complex memberships
Star-PAP complexU2 snRNP

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 RBM10 binds to pre-mRNAs in the vicinity of splice sites and regulates exon skipping; PAR-CLIP identified thousands of RBM10 binding sites, and loss-of-function/gain-of-function experiments validated a mechanistic model of RBM10-mediated splicing regulation confirmed by minigene experiments. PAR-CLIP, loss-of-function and gain-of-function experiments, minigene assays EMBO molecular medicine High 24000153
2014 RBM10 regulates alternative splicing of Fas pre-mRNA (promoting exon skipping) and Bcl-x pre-mRNA (selection of internal 5'-splice site), with a proposed consensus RBM10-binding sequence at 5'-splice sites of target exons. Splicing assays, binding site analysis, functional knockdown/overexpression FEBS letters Medium 24530524
2016 RBM10 promotes exon skipping of NUMB exon 9, generating a Notch signaling repressor isoform; the RRM1-ZnF module recognizes a GGA-centered motif in exonic sites, while RRM2 recognizes a C-rich intronic sequence near the NUMB exon 9 3' site. An oncogenic V354E mutation in RRM2 does not disrupt RNA binding to NUMB sequences but disrupts splicing regulation activity. RNA binding assays, structural modeling, mutagenesis, splicing reporter assays RNA biology High 26853560
2017 RBM10's RRM1-ZnF unit recognizes a GGA-centered motif in exonic binding sites with high affinity and specificity to promote exon skipping; RRM2 recognizes a C-rich intronic sequence contributing to NUMB exon 9 regulation, explaining RBM10's broad RNA specificity through two distinct RNA-binding units. Biochemical RNA binding assays, structural analysis, splicing reporter assays Nucleic acids research High 28379442
2017 A polypeptide containing RRM1, ZnF1, and RRM2 of RBM10 cooperatively recognizes Fas exon 6 mRNA with ~20 nM affinity, far higher than individual domains (micromolar); NMR structures of RRM1, ZnF1, and the V354del isoform of RRM2 confirmed canonical RNA recognition elements. NMR structure determination, RNA binding assays with domain combinations Biochemistry High 29450990
2015 NMR structure of the RBM10 OCRE domain revealed it forms a 55-residue globular domain with an anti-parallel arrangement of six β-strands containing tyrosine triplets, representing a distinctive structural module conserved in RBM10 across the animal kingdom that mediates intermolecular interactions in the spliceosome. NMR structure determination Structure High 26712279
2017 RBM10 negatively autoregulates its own mRNA and protein expression, and cross-regulates its paralog RBM5, by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD) via skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5. Computational analysis, experimental validation of AS-NMD events, splicing assays Nucleic acids research High 28586478
2016 RBM10 binds pre-mRNAs with significant enrichment in intronic regions in mouse embryonic mandibular cells (iCLIP); RBM10 KO leads to alternative splicing changes in transcripts directly bound by RBM10, and depletion of RBM10 in mouse ES cells causes proliferation defects and gross alterations in differentiation potential. iCLIP, RNA-seq, RBM10 KO mouse cells RNA biology High 27763814
2018 RBM10 has a splicing-independent function: it associates with the non-canonical poly(A) polymerase Star-PAP (TUT1) via the RBM10 RRM2 domain binding the Star-PAP catalytic domain, binds the pre-mRNA 3' UTR, and directs Star-PAP complex assembly onto mRNAs encoding anti-hypertrophy regulators to control their polyadenylation and expression in cardiac cells. Co-immunoprecipitation, domain binding assays, functional knockdown/overexpression in cardiomyoblasts and rat hearts Cell reports High 30257214
2024 RBM10 and RBM5 are subunits of the U2 snRNP engaged with intron branch sites on chromatin in precatalytic A/B-like spliceosomes; a conserved peptide segment including a zinc finger motif is required for their U2 snRNP interaction, and deletion of this segment renders RBM10 inactive for repression of many alternative exons. Isolation of chromatin-associated spliceosome complexes, proteomics, branch-site sequencing, deletion mutagenesis Molecular cell High 38537639
2017 RBM10 controls appropriate splicing of Dnmt3b isoforms: RBM10 deficiency increases enzymatically active Dnmt3b2 and decreases Dnmt3b3 (inactive), leading to increased DNA methylation of NF-κB-responsive gene promoters and suppression of NF-κB-mediated transcription and inflammatory responses. In vivo mouse models, in vitro splicing assays, promoter methylation analysis, NF-κB reporter assays International immunology Medium 29309623
2022 RBM10 modulates alternative splicing of Bcl-x to regulate the ratio of proapoptotic Bcl-xS to antiapoptotic Bcl-xL; RBM10 deficiency decreases this ratio, diminishing EGFR inhibitor-mediated apoptosis in EGFR-mutant lung cancer cells. Patient-derived tumor models, genetic inactivation of RBM10, splicing analysis, apoptosis assays The Journal of clinical investigation High 35579943
2020 Dengue NS5 polymerase interacts with RBM10 and triggers its proteasome-mediated degradation; RBM10 promotes exon 4 skipping in SAT1 pre-mRNA (an antiviral gene), and RBM10 interacts with viral RNA and RIG-I, promoting RIG-I ubiquitination (a key activation step for innate immune signaling). Co-immunoprecipitation, RNA-seq, proteasome inhibitor rescue, RIG-I ubiquitination assays, overexpression/knockdown functional assays Nucleic acids research High 32432721
2016 RBM10 is identified as a FilGAP-interacting protein; Src family kinase Fyn activity induces translocation of RBM10 from nucleus to cell periphery, where it co-localizes with FilGAP. RBM10 is required for peripheral localization of FilGAP and for FilGAP-mediated suppression of Rac activity and cell spreading. Co-immunoprecipitation, fluorescence microscopy, siRNA knockdown, cell spreading assays PloS one Medium 26751795
2013 RBM10 contains three nuclear localization sequences (NLS1 at aa 743-759 bipartite, NLS2 in the RRM1 region aa 60-136, NLS3 in the OCRE region aa 481-540) that act cooperatively; removal of all NLSs results in complete cytoplasmic localization. The OCRE domain functions as a novel NLS motif. Deletion and substitution mutagenesis, EGFP/FLAG-fusion localization assays Biology of the cell Medium 23294349
2021 RBM10 is sequestered in nuclear bodies (S1-1 NBs) via two NB-targeting sequences (NBTS): one in the KEKE motif region and one in the C2H2 Zn finger; the C2H2 ZnF is also essential for alternative splicing regulation. NB-localization increases when cellular transcriptional activity declines, suggesting NB sequestration regulates RBM10 splicing activity. Deletion mutagenesis, live-cell imaging, transcription inhibition experiments International journal of molecular sciences Medium 34638866
2020 RBM10 overexpression in HepG2 cells causes ectopic assembly of PLK4-STIL complexes in the nucleus, depleting centrosomal PLK4 and STIL, thereby impairing centriole duplication and causing M-phase arrest with monopolar spindles. This effect requires nuclear localization of RBM10 and is independent of its alternative splicing function. RBM10 KO cell lines, doxycycline-inducible re-expression, immunofluorescence, cell cycle analysis, NES-forced cytoplasmic mutant Genes to cells Medium 31820547
2019 RBM10 inhibits cell proliferation in lung adenocarcinoma via the RAP1/AKT/CREB signaling pathway; RBM10 overexpression decreases RAP1 activation, and EPAC stimulation/inhibition abolishes effects of RBM10 knockdown/overexpression respectively. This effect is independent of MAPK/ERK and P38/MAPK pathways. cDNA microarray, EPAC pharmacological modulation, signaling pathway analysis, in vitro and in vivo proliferation assays Journal of cellular and molecular medicine Medium 30955253
2021 RBM10 binds Star-PAP target mRNAs globally; knockdown of RBM10 results in global loss of Star-PAP association on target mRNAs and compromises 3'-end processing of a set of Star-PAP target mRNAs while regulating stability/turnover of others, establishing RBM10-RNA association as required for Star-PAP mRNA targeting. HITS-CLIP, mRNA stability assays, RBM10 knockdown with Star-PAP association measurements International journal of molecular sciences Medium 34576144
2024 cSrc kinase phosphorylates RBM10 at three tyrosine residues (Y81, Y500, Y971); this phosphorylation is induced during cardiac hypertrophy and is required for RBM10 nuclear localization and interaction with Star-PAP, enabling anti-hypertrophy gene expression. Loss of phosphorylation (cSrc inhibition or Y→F mutation) prevents RBM10 from reversing cardiomyocyte hypertrophy. In vitro kinase assays, phospho-deficient mutants, isoproterenol rat hypertrophy model, nuclear localization assays, Co-IP Life sciences Medium 38309577
2024 RBM10 has a splicing-independent role in regulating DNA replication fork progression and replication stress response; RBM10 interacts with active DNA replication forks via PRIM1, recruits HDAC1 to facilitate H4K16 deacetylation, and maintains R-loop homeostasis to stabilize replication forks. WEE1 is a synthetic lethal partner of RBM10 loss identified by CRISPR screen. CRISPR-Cas9 synthetic lethality screen, replication fork assays, Co-IP with replication factors, H4K16ac ChIP, R-loop analysis, in vitro and in vivo WEE1 inhibition Nature communications High 39080280
2017 RBM5 post-transcriptionally regulates RBM10 expression via direct interaction with specific RBM10 splice variants, as demonstrated by RNA immunoprecipitation followed by next-generation sequencing (RIP-Seq) in SCLC cells. RIP-Seq, Western blotting PloS one Medium 28662214
2023 RBM10 recruits METTL3 to inhibit m6A methylation of MALAT1; RBM10 directly binds MALAT1 (confirmed by CLIP-Seq and RIP), and this interaction affects PI3K/AKT/mTOR phosphorylation to inhibit invasion and migration of NSCLC cells. CLIP-Seq, RNA immunoprecipitation, MeRIP-qPCR, Transwell/wound-healing assays, rescue experiments Life sciences Medium 36608868
2022 RBM10 regulates alternative splicing of lncRNA Neat1 to promote Neat1_1 over Neat1_2; RBM10 binds Neat1 (confirmed by CLIP-Seq/RIP), and suppresses PI3K/AKT/mTOR pathway activation via Neat1_2, inhibiting NSCLC invasion and metastasis. CLIP-Seq, RNA immunoprecipitation, RT-qPCR, Transwell invasion assay, Western blot Cancer cell international Medium 36335386
2025 RBM10 loss causes exon inclusion events in transcripts for cytoskeletal and ECM regulators VCL, TNC, and CD44; this leads to RAC1-GTP activation and metastatic competency. Knockdown of individual exon-inclusion isoforms in RBM10-null cells reverses cell velocity (VCL) or invasiveness (TNC, CD44), and combined knockdown reverses metastases in mouse HrasG12V/Rbm10KO thyrocytes. Transcriptomic analysis, targeted knockdown of splicing isoforms, RAC1-GTP pull-down, in vivo mouse thyroid cancer model The Journal of experimental medicine High 39992626
2024 RBM10 forms a triple complex with YBX1 and the phosphatase PPM1B; RBM10 knockdown reduces YBX1-PPM1B association, leading to elevated YBX1 phosphorylation and nuclear translocation, promoting cancer cell proliferation and migration. PPM1B overexpression rescues the tumorigenic phenotypes caused by RBM10 depletion. Co-immunoprecipitation, phosphorylation assays, nuclear fractionation, rescue experiments with PPM1B overexpression Experimental cell research Medium 38246397
2024 RBM10 C761Y mutation in the C2H2-type zinc finger domain impairs its interaction with splicing factor SRSF2, preventing RBM10-mediated ASPM exon 18 skipping; the resulting ASPM203 isoform stabilizes DVL2 and activates β-catenin/Wnt signaling to promote cholangiocarcinoma progression. Minigene splicing reporter, co-immunoprecipitation, RNA sequencing, functional cancer assays Journal of experimental & clinical cancer research Medium 38576051
2025 HIV-1 Vpu interacts with RBM10 and promotes its degradation through the ubiquitin-proteasome pathway; RBM10 inhibits HIV-1 replication by binding to viral RNA and reducing incompletely spliced HIV-1 transcripts, and also promotes transcription of antiviral genes. APEX2-proximity labeling/mass spectrometry, IP-MS, ubiquitin-proteasome pathway inhibition, RNA binding assays mSystems Medium 40742131
2021 In fission yeast, Rbm10 (ortholog of human RBM10) associates with the histone deacetylase Clr6 complex and chromatin remodelers; Rbm10 deletion causes severe heterochromatin defects with significant reduction of Clr6 in heterochromatin, establishing a splicing-independent role in heterochromatin assembly. Proteomics, ChIP-seq, deep sequencing, yeast genetics Epigenetics & chromatin Medium 33468217
2021 RBM10 regulates splicing of the human TERT gene, promoting exclusion of exons 7 and 8 to produce a non-functional hTERT-s isoform; RBM10 binding to TERT pre-mRNA was confirmed by RNA-IP and RNA pull-down assays, and RBM10 overexpression suppresses telomerase activity in pancreatic cancer. RNA-IP, RNA pull-down, minigene splicing assay, telomerase activity assay, xenograft models American journal of cancer research Medium 33520366
2025 RBM10 directly binds intronic flanking regions of circHIPK3 and circSMARCA5 (PAR-CLIP and RNA pulldown); RBM10 binding to the 3' flanking region promotes exon skipping and circularization more efficiently than 5' binding, and interacts with SF3B1 as an upstream event governing circRNA biogenesis. Loss of RBM10 reduces these circRNAs and promotes tumorigenesis. PAR-CLIP, RNA pulldown, splicing reporter assay, Co-IP (RBM10-SF3B1), RNA-seq, functional cancer assays Biomarker research Medium 41673707

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. American journal of human genetics 131 20451169
2017 Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence. Clinical cancer research : an official journal of the American Association for Cancer Research 108 28634282
2017 RBM10-TFE3 Renal Cell Carcinoma: A Potential Diagnostic Pitfall Due to Cryptic Intrachromosomal Xp11.2 Inversion Resulting in False-negative TFE3 FISH. The American journal of surgical pathology 106 28296677
2016 Tumor suppressor properties of the splicing regulatory factor RBM10. RNA biology 96 26853560
2013 Integrative analysis revealed the molecular mechanism underlying RBM10-mediated splicing regulation. EMBO molecular medicine 93 24000153
2017 Functional analysis reveals that RBM10 mutations contribute to lung adenocarcinoma pathogenesis by deregulating splicing. Scientific reports 78 28091594
2023 Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines 75 37509501
2006 Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer. Journal of cellular biochemistry 72 16552754
2014 RBM10 regulates alternative splicing. FEBS letters 64 24530524
2020 Dengue virus targets RBM10 deregulating host cell splicing and innate immune response. Nucleic acids research 58 32432721
2011 Long-term survival in TARP syndrome and confirmation of RBM10 as the disease-causing gene. American journal of medical genetics. Part A 54 21910224
2022 Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer. The Journal of clinical investigation 51 35579943
2017 Xp11 Translocation Renal Cell Carcinomas (RCCs) With RBM10-TFE3 Gene Fusion Demonstrating Melanotic Features and Overlapping Morphology With t(6;11) RCC: Interest and Diagnostic Pitfall in Detecting a Paracentric Inversion of TFE3. The American journal of surgical pathology 51 28288037
2017 Autoregulation of RBM10 and cross-regulation of RBM10/RBM5 via alternative splicing-coupled nonsense-mediated decay. Nucleic acids research 48 28586478
2016 The RNA-binding landscape of RBM10 and its role in alternative splicing regulation in models of mouse early development. RNA biology 45 27763814
2019 RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway. Journal of cellular and molecular medicine 42 30955253
2018 A Splicing-Independent Function of RBM10 Controls Specific 3' UTR Processing to Regulate Cardiac Hypertrophy. Cell reports 42 30257214
2021 RBM10: Structure, functions, and associated diseases. Gene 41 33515724
2019 RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review. Histopathology 36 30908700
2017 An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion. Nucleic acids research 36 28379442
2021 RBM10 Regulates Tumor Apoptosis, Proliferation, and Metastasis. Frontiers in oncology 35 33718153
2018 RBM10: Harmful or helpful-many factors to consider. Journal of cellular biochemistry 34 29274279
2017 RBM10 promotes transformation-associated processes in small cell lung cancer and is directly regulated by RBM5. PloS one 33 28662214
2016 Identification by FFPE RNA-Seq of a new recurrent inversion leading to RBM10-TFE3 fusion in renal cell carcinoma with subtle TFE3 break-apart FISH pattern. Genes, chromosomes & cancer 33 26998913
2023 RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition. Cancer research 32 36853175
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2020 miR-335 modulates Numb alternative splicing via targeting RBM10 in endometrial cancer. The Kaohsiung journal of medical sciences 30 31894898
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2019 Alternative splicing of VEGFA is regulated by RBM10 in endometrial cancer. The Kaohsiung journal of medical sciences 23 31587503
2024 The splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin. Molecular cell 22 38537639
2017 Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration. BMC medical genetics 20 28577551
2022 RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC. Cancer cell international 19 36335386
2017 Splicing arrays reveal novel RBM10 targets, including SMN2 pre-mRNA. BMC molecular biology 17 28728573
2021 Phenotypic spectrum of the RBM10-mediated intellectual disability and congenital malformation syndrome beyond classic TARP syndrome features. Clinical genetics 16 33340101
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2015 Nuclear Magnetic Resonance Structure of a Novel Globular Domain in RBM10 Containing OCRE, the Octamer Repeat Sequence Motif. Structure (London, England : 1993) 16 26712279
2013 S1-1/RBM10: multiplicity and cooperativity of nuclear localisation domains. Biology of the cell 16 23294349
2023 RBM10 recruits METTL3 to induce N6-methyladenosine-MALAT1-dependent modification, inhibiting the invasion and migration of NSCLC. Life sciences 15 36608868
2013 Differential downregulation of Rbm5 and Rbm10 during skeletal and cardiac differentiation. In vitro cellular & developmental biology. Animal 15 24178303
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2017 Increased cell apoptosis in human lung adenocarcinoma and in vivo tumor growth inhibition by RBM10, a tumor suppressor gene. Oncology letters 14 29085465
2008 The small variant of the apoptosis-associated X-chromosome RBM10 gene is co-expressed with caspase-3 in breast cancer. Cancer genomics & proteomics 13 18820371
2022 NPTX1 inhibits pancreatic cancer cell proliferation and migration and enhances chemotherapy sensitivity by targeting RBM10. Oncology letters 12 35836482
2020 Protective effect of the RNA-binding protein RBM10 in hepatocellular carcinoma. European review for medical and pharmacological sciences 12 32572914
2024 RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma. Journal of experimental & clinical cancer research : CR 11 38576051
2020 A novel missense variant in RBM10 can cause a mild form of TARP syndrome with developmental delay and dysmorphic features. Clinical genetics 11 32812661
2023 An RBM10 and NF-κB interacting host lncRNA promotes JEV replication and neuronal cell death. Journal of virology 10 37991381
2021 Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex. Epigenetics & chromatin 10 33468217
2018 Splicing Site Recognition by Synergy of Three Domains in Splicing Factor RBM10. Biochemistry 10 29450990
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2021 RBM10-TFE3 fusions: A FISH-concealed anomaly in adult renal cell carcinomas displaying a variety of morphological and genomic features: Comprehensive study of six novel cases. Genes, chromosomes & cancer 9 34358382
2024 Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma. Nature communications 8 39080280
2021 Star-PAP RNA Binding Landscape Reveals Novel Role of Star-PAP in mRNA Metabolism That Requires RBM10-RNA Association. International journal of molecular sciences 7 34576144
2020 RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4-STIL complexes in the nucleus. Genes to cells : devoted to molecular & cellular mechanisms 7 31820547
2021 Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance. International journal of molecular sciences 6 34638866
2025 RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs. The Journal of experimental medicine 4 39992626
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2019 RBM10 truncation in astroblastoma in a patient with history of mandibular ameloblastoma: A case report. Cancer genetics 4 30803556
2025 RBM10 deficiency promotes brain metastasis by modulating sphingolipid metabolism in a BBB model of EGFR mutant lung adenocarcinoma. Journal of experimental & clinical cancer research : CR 3 40069781
2023 The apoptotic splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin. bioRxiv : the preprint server for biology 3 37790489
2020 OCRE Domains of Splicing Factors RBM5 and RBM10: Tyrosine Ring-Flip Frequencies Determined by Integrated Use of 1 H NMR Spectroscopy and Molecular Dynamics Simulations. Chembiochem : a European journal of chemical biology 3 32975902
2025 Targeting RBM10-Repressed RORB Activity in Liquid Condensates Inhibits Lysosomal Biogenesis and Neuroblastoma Progression via Affecting NF-κB Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 40899609
2024 RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities. Experimental cell research 2 38246397
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2023 Functional insight into a neurodevelopmental disorder caused by missense variants in an RNA-binding protein, RBM10. Journal of human genetics 2 37268768
2022 Conjunctival Perivascular Epithelioid Cell Neoplasm With RBM10-TFE3 Fusion Presenting as Recurrent Subconjunctival Hemorrhage. Ophthalmic plastic and reconstructive surgery 2 36095845
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2024 Down regulation of RBM10 promotes proliferation and metastasis via miR-224-5p/RBM10/p53 feedback loop in lung adenocarcinoma. Heliyon 1 39144991
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2026 Fatal Disease Progression Driven by Acquired MET Amplification After EGFR-TKI Therapy in EGFR- and RBM10-Mutant Lung Adenocarcinoma. Cancer management and research 0 41878697
2026 Frequent RBM10 Comutation and a Mutually Exclusive Relationship With Other TP53 Pathway Aberrations in Early-Stage Non-Small-Cell Lung Cancer with EGFR Mutation. Clinical lung cancer 0 41934032
2025 Splicing factor RBM10 loss fuels thyroid cancer metastasis. The Journal of experimental medicine 0 39992625
2025 RBM10 suppresses malignant transformation in endometrial cancer via the Hippo-YAP signaling pathway. American journal of translational research 0 40092130
2025 Gastric carcinoma harbouring loss‑of‑function mutations in the PIK3R1, ATRX and RBM10 genes exhibits diverse histological features associated with EBV infection and TP53 inactivation: A case report. Oncology letters 0 40213088
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2024 Investigation of RBM10 mutation and its associations with clinical and molecular characteristics in EGFR-mutant and EGFR-wildtype lung adenocarcinoma. Heliyon 0 38912481