Affinage

SRSF10

Serine/arginine-rich splicing factor 10 · UniProt O75494

Length
262 aa
Mass
31.3 kDa
Annotated
2026-06-10
47 papers in source corpus 33 papers cited in narrative 34 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

SRSF10 is an atypical SR-family splicing regulator whose function is switched by phosphorylation state, allowing it to act either as a general splicing repressor or as a sequence-specific splicing activator that shapes broad alternative-splicing networks across development and stress (PMID:12419250, PMID:18794844). In its dephosphorylated form it is a potent general repressor that blocks splicing at an early step, acting through its RNA-binding domain and an interaction with U1 snRNP that interferes with 5'-splice-site recognition (PMID:12419250, PMID:16135820); this dephosphorylated, repressive state is induced specifically in mitosis and upon heat shock (PMID:12419250, PMID:14765198). The conversion is executed by PP1, which is recruited to the SRSF10 RS domain and activated by NIPP1 dissociation, while 14-3-3 binding protects SRSF10 from dephosphorylation under non-stress conditions and Hsp27 drives rephosphorylation during recovery (PMID:17936706, PMID:21135127). When phosphorylated, SRSF10 instead stabilizes U1/U2 snRNP engagement with pre-mRNA and functions as a sequence-specific activator, with CK1ε phosphorylating S23 and S133 to license target-mRNA binding (PMID:18794844, PMID:40701249). Through position-dependent binding—promoting cassette-exon inclusion when bound to the exon and exclusion when bound downstream—SRSF10 controls defined splicing programs essential for cardiac Ca2+ handling via triadin, adipogenesis via lipin1α, myogenesis via Lrrfip1, hepatic glucose output via PGC1α, spermatogonial expansion, oligodendrocyte differentiation via Myo5a, and cortical neurogenesis (PMID:24442672, PMID:19386262, PMID:24710272, PMID:26586428, PMID:36355419, PMID:40439883, PMID:37360696). Upon DNA damage, SRSF10 dephosphorylation rewires its assembly with hnRNP K, hnRNP F/H, Sam68 and 14-3-3ε on the Bcl-x pre-mRNA to shift splicing toward the pro-apoptotic Bcl-xS isoform (PMID:27851963, PMID:29396485). SRSF10 is co-opted in multiple cancers, where it controls oncogenic isoform choices such as BCLAF1 exon 5a, CDC25A and MDM4 exons, and modulates the tumor microenvironment (PMID:25091051, PMID:36539837, PMID:38113691), and it restricts viral pathogens including HBV and HIV-1 in a phosphorylation-dependent manner (PMID:33180834, PMID:27928057).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established that SRSF10 is not a constitutive splicing factor but a phosphorylation-gated general repressor, defining the central regulatory logic of the protein.

    Evidence In vitro splicing assays with defined phosphorylation states, immunodepletion, and cell-cycle synchronization

    PMID:12419250

    Open questions at the time
    • Did not define the snRNP target or step of repression
    • Phosphatase/kinase machinery unidentified
  2. 2004 High

    Identified the mechanistic basis of repression and a physiological trigger, showing dephosphorylated SRSF10 binds U1 snRNP to block 5'-splice-site recognition during heat shock.

    Evidence In vitro splicing reconstitution, U1 snRNP co-IP, and SRSF10-knockout DT40 cells

    PMID:14765198

    Open questions at the time
    • Precise contact between SRSF10 and U1 components not structurally resolved
    • Whether other snRNPs contribute left open
  3. 2005 High

    Localized repressive activity to the RNA-binding domain and mapped RS subdomain functions, distinguishing SRSF10 from activating SR proteins like SC35.

    Evidence Immunofluorescence colocalization with snRNPs, deletion mutants, and SRSF10/SC35 chimeras in vitro

    PMID:16135820

    Open questions at the time
    • Structural basis of RBD-mediated repression not determined
  4. 2007 High

    Defined the enzymatic switch controlling SRSF10, identifying PP1 as the phosphatase, NIPP1 as its regulator, and 14-3-3 as a protective binding partner.

    Evidence In vitro phosphatase assays, domain-mapped PP1 recruitment to the RS domain, and 14-3-3 co-IP

    PMID:17936706

    Open questions at the time
    • Identity of the relevant SR protein kinase(s) under basal conditions not fully resolved here
    • How 14-3-3 dissociation is signaled unclear
  5. 2005 Medium

    Showed how cells reverse the repressive state, with Hsp27 promoting SRSF10 rephosphorylation to restore splicing after heat shock.

    Evidence Hsp27/alphaB-crystallin expression, phosphorylation immunoblotting, and pharmacological phosphatase inhibition

    PMID:16339078

    Open questions at the time
    • The kinase enabling rephosphorylation not identified
    • Single-lab functional assay
  6. 2010 Medium

    Demonstrated that Hsp27 acts via direct binding to SRSF10 and that thermotolerance protects SRSF10 from dephosphorylation, linking stress memory to splicing control.

    Evidence Hsp27-SRSF10 co-IP, overexpression, and in vitro splicing assays requiring de novo protein synthesis

    PMID:21135127

    Open questions at the time
    • Mechanism by which Hsp27 binding favors rephosphorylation undefined
    • Single lab
  7. 2008 High

    Revealed the second functional state, showing phosphorylated SRSF10 is a sequence-specific activator that stabilizes U1/U2 snRNP recognition—uniquely bifunctional among SR proteins.

    Evidence In vitro splicing with defined phospho-states, spliceosome complex assembly analysis, and U1/U2 binding assays

    PMID:18794844

    Open questions at the time
    • Cofactor required for complex B/C progression not identified
    • Sequence determinants of specific binding not yet mapped genome-wide
  8. 2009 High

    Provided the first in vivo demonstration of a physiological splicing target, linking SRSF10 to triadin splicing and cardiac Ca2+ handling.

    Evidence SRSF10-null mice, direct binding to the regulated triadin exon, in vitro splicing, and cardiomyocyte Ca2+ imaging

    PMID:19386262

    Open questions at the time
    • Phosphorylation state of SRSF10 governing this target not specified
    • Other cardiac targets not catalogued
  9. 2014 High

    Defined the position-dependent splicing code of SRSF10 transcriptome-wide and tied its activity to stress-induced apoptosis resistance.

    Evidence RNA-seq, minigene mutagenesis of binding motifs, and SRSF10 knockout/reconstitution viability assays

    PMID:24442672

    Open questions at the time
    • Did not resolve how the same binding event yields opposite outcomes mechanistically
  10. 2014 High

    Extended the in vivo target network to metabolic and growth programs, establishing lipin1α (adipogenesis) and a pro-tumorigenic BCLAF1 isoform as SRSF10 outputs.

    Evidence SRSF10-null mice with rescue, minigene splicing, cis-element binding, and colorectal cancer knockdown/growth assays

    PMID:24710272 PMID:25091051

    Open questions at the time
    • Tissue-specific determinants of target selection unclear
    • BCLAF1 study is Medium confidence single-lab
  11. 2015 High

    Broadened the physiological splicing program to muscle and liver, with Lrrfip1 driving myogenesis and PGC1α regulation controlling hepatic glucose output.

    Evidence Conditional KO mice, RNA-seq, minigene assays, and glucose production assays

    PMID:26586428

    Open questions at the time
    • Upstream signals selecting these tissue-specific targets undefined
  12. 2016 High

    Connected the DNA-damage response to apoptotic splicing decisions, showing damage-induced SRSF10 dephosphorylation rewires hnRNP K and hnRNP F/H interactions on Bcl-x toward Bcl-xS.

    Evidence Reciprocal RIP/co-IP, ATM/CHK2 inhibition, minigene assays, and RNA-seq

    PMID:27851963

    Open questions at the time
    • Direct phosphatase acting on SRSF10 after damage not identified here
  13. 2018 Medium

    Resolved the multi-protein assembly underlying damage-induced Bcl-x switching, adding 14-3-3ε, hnRNP A1/A2 and Sam68 to the regulatory complex.

    Evidence RNA affinity pulldown and co-IP with siRNA functional validation

    PMID:29396485

    Open questions at the time
    • Order of assembly and direct vs. bridged contacts not fully resolved
    • Single lab
  14. 2017 Medium

    Established SRSF10 as a druggable host splicing factor for viral infection, with compound 1C8 promoting its dephosphorylation to reduce HIV-1 splicing.

    Evidence RNAi, phosphorylation immunoblotting, hTra2β co-IP, and RT-PCR of HIV-1 splice variants

    PMID:27928057

    Open questions at the time
    • Direct SRSF10 binding sites on HIV-1 RNA not mapped
    • Single lab
  15. 2020 Medium

    Expanded SRSF10's antiviral and clinically relevant target repertoire, including HBV restriction, SMN2 exon 7 inclusion, and avian ANP32A isoform control of influenza polymerase.

    Evidence HBc interactome proteomics with KD, SPR/MS direct-binding to ISS-N1 with splice-switching oligos, and RNA affinity/RIP for ANP32A

    PMID:32574681 PMID:33180834 PMID:33300159

    Open questions at the time
    • HBV effect is on nascent RNA level rather than splicing and mechanism unresolved
    • Isoform-length dependence of SMN regulation not fully explained
  16. 2021 Medium

    Identified non-coding RNA control of SRSF10 activity and a kinase upstream of its activating phosphorylation, with circRNA cTTN1 binding SRSF10 and CLK1/4 inhibition impairing its splicing function.

    Evidence RIP in iPSC-cardiomyocytes, GPS167/192 CLK inhibition with co-IP, and minigene/apoptosis assays

    PMID:33583186 PMID:34316707

    Open questions at the time
    • Whether circRNA acts by sequestration or presentation not definitively distinguished
    • CLK phosphosite specificity not mapped in these studies
  17. 2022 High

    Demonstrated essential roles in spermatogonial expansion and consolidated SRSF10 as an oncogenic splicing driver acting through CDC25A and SREK1/B-T circuits.

    Evidence Germ-cell KO mice with iRIP-seq, plus RIP/CLIP and isoform mutagenesis in HCC models

    PMID:35296659 PMID:36355419 PMID:36539837

    Open questions at the time
    • Phospho-state dependence of germline targeting not addressed
    • HCC mechanisms are Medium-confidence single-lab
  18. 2025 High

    Defined CK1ε as a direct kinase phosphorylating SRSF10 at S23/S133 to enable target-mRNA binding, and extended developmental roles to oligodendrocyte differentiation via Myo5a splicing.

    Evidence In vitro kinase assay with phosphosite mapping and epistasis; OLC-specific conditional KO with RIP-seq and ASO rescue

    PMID:40439883 PMID:40701249

    Open questions at the time
    • Relationship between CK1ε and previously implicated SR kinases unclear
    • Whether S23/S133 phosphorylation governs all activating functions not tested broadly

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single phosphorylation switch and position-dependent binding code are integrated to select among hundreds of tissue- and stress-specific targets remains unresolved.
  • No structural model of the SRSF10–U1/U2 or SRSF10–pre-mRNA complexes
  • Upstream signaling that directs target choice in each tissue not defined
  • Kinase/phosphatase partners not unified into a single quantitative model

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0048018 receptor ligand activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-8953854 Metabolism of RNA 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
14-3-3CK1ΕHNRNP F/HHNRNP KHSP27PP1SAM68U1 SNRNP

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SRp38 (SRSF10) is a general splicing repressor when dephosphorylated; in its phosphorylated form it is essentially inactive in splicing assays. Dephosphorylation converts it to a potent, general repressor that inhibits splicing at an early step. SRp38 is specifically dephosphorylated in mitotic cells and is required for splicing repression observed in mitotic cell extracts. In vitro splicing assays, immunodepletion, cell-cycle synchronization, phosphorylation-state analysis Cell High 12419250
2004 SRp38 (SRSF10) is dephosphorylated upon heat shock, and dephosphorylated SRp38 is required for heat-shock-induced splicing repression. Depletion of SRp38 from heat-shocked extracts derepresses splicing; adding back dephosphorylated SRp38 restores inhibition. Dephosphorylated SRp38 interacts with U1 snRNP protein and interferes with 5'-splice-site recognition by U1 snRNP. SRp38-deficient DT40 cells show altered cell-cycle profile and are temperature sensitive. In vitro splicing assays, immunodepletion/reconstitution, co-immunoprecipitation with U1 snRNP, SRp38-knockout DT40 cells Nature High 14765198
2005 Dephosphorylated SRp38 redistributes and colocalizes with snRNPs (but not SC35) during mitosis and after heat shock. An snRNP component fully rescues heat-shock-induced splicing repression in vitro; purified U1 snRNP does so partially. The RS domain of SRp38 contains two subdomains (RS1 and RS2): RS1 deletion mutant specifically inhibits the second step of splicing, while RS2 deletion retains dephosphorylation-dependent repression. The RBD of SRp38 is responsible for repression activity whereas the RS domain of SC35 confers activation. Immunofluorescence, in vitro splicing assays with deletion mutants, chimeric SRp38/SC35 constructs, snRNP rescue experiments Molecular and cellular biology High 16135820
2007 SRp38 dephosphorylation upon heat shock is carried out by the phosphatase PP1, which is activated by dissociation of its inhibitor NIPP1. PP1 is targeted to SRp38 through a direct interaction via SRp38's RS domain. The specific dephosphorylation of SRp38 (and not other SR proteins) is largely determined by the low activity of SR protein kinases toward SRp38. Under non-stress conditions, 14-3-3 proteins associate with SRp38 and protect it from dephosphorylation; upon heat shock, 14-3-3 dissociates. In vitro phosphatase assay, co-immunoprecipitation, domain mapping, kinase activity assays, immunoblotting Molecular cell High 17936706
2005 Hsp27 (but not alphaB-crystallin) enhances rephosphorylation of SRp38 after heat shock, thereby promoting recovery of splicing. This requires phosphorylatable Hsp27 and a Hsp90 client protein. Hsp27 does not prevent dephosphorylation of SRp38 during heat shock. Calyculin A (phosphatase inhibitor) prevents SRp38 dephosphorylation during heat shock, indicating cells recovering from heat shock are not kinase-deficient. Exogenous expression of Hsp27/alphaB-crystallin, immunoblotting for SRp38 phosphorylation, in vitro splicing assays, pharmacological inhibition Molecular biology of the cell Medium 16339078
2008 Phosphorylated SRp38 (SRSF10) functions as a sequence-specific splicing activator, unlike all other characterized SR proteins. It can induce spliceosome complex A formation without a cofactor, but requires a cofactor for progression to complexes B and C. Phosphorylated SRp38 strengthens stable recognition of pre-mRNA by U1 and U2 snRNPs. SRp38 was shown to alter alternative splicing of glutamate receptor B pre-mRNA in a sequence-specific manner. In vitro splicing assays, spliceosomal complex assembly analysis, minigene splicing, U1/U2 snRNP binding assays Nature structural & molecular biology High 18794844
2009 SRp38 (SRSF10) null mice die mostly by E15.5 with cardiac defects. In the embryonic heart, SRp38 regulates alternative splicing of cardiac triadin pre-mRNA; absence of SRp38 reduces triadin protein and interacting protein calsequestrin 2. Purified SRp38 binds specifically to the regulated triadin exon and modulates triadin splicing in vitro. SRp38-null embryonic cardiomyocytes exhibit defective Ca2+ handling. Knockout mouse, RNA profiling, in vitro splicing assay with purified SRp38, RNA binding (direct binding to regulated exon), Ca2+ imaging in isolated cardiomyocytes Developmental cell High 19386262
2010 A mild heat pretreatment (thermotolerance) protects SRSF10 from dephosphorylation during a subsequent severe heat shock, and this requires de novo protein synthesis. Hsp27 overexpression inhibits SRSF10 dephosphorylation by directly interacting with SRSF10, thereby preventing splicing repression. Immunoblotting for SRSF10 phosphorylation, overexpression of Hsp27, co-immunoprecipitation of Hsp27-SRSF10, in vitro splicing assays Molecular and cellular biology Medium 21135127
2014 SRSF10 stimulates inclusion of BCLAF1 alternative exon 5a in a sequence-specific manner, producing a pro-tumorigenic BCLAF1 protein isoform. SRSF10 knockdown inhibits growth of colorectal cancer cells and reduces exon 5a inclusion. Minigene splicing assays, siRNA knockdown, RT-PCR for isoform quantification, cell growth assays Nature communications Medium 25091051
2014 SRSF10 promotes both exon inclusion and exclusion in a position-dependent manner: binding to cassette exons promotes inclusion, whereas binding within downstream constitutive exons promotes exclusion. This positional effect was validated by mutagenesis of SRSF10 binding motifs in minigene constructs. Cells depleted of SRSF10 are more susceptible to ER stress-induced apoptosis; reconstitution of SRSF10 in KO cells rescues wild-type splicing and stress resistance. RNA-seq coupled with bioinformatics, minigene mutagenesis, SRSF10 knockout and reconstitution, cell viability assays Nucleic acids research High 24442672
2014 SRSF10 controls alternative splicing of lipin1 pre-mRNA by binding a cis-element in constitutive exon 8 to promote skipping of exon 7, generating the lipin1α isoform required for early adipocyte differentiation. SRSF10-null mice display severely impaired subcutaneous white adipose tissue development. Lipin1α expression rescues adipogenic defects caused by SRSF10 loss. SRSF10 knockout mice, RNA-seq, minigene splicing assays, cis-element binding analysis, adipocyte differentiation assays, rescue experiments Molecular and cellular biology High 24710272
2015 SRSF10 activates inclusion of alternative exons 16 and 17 of Lrrfip1 in muscle, an event essential for myoblast differentiation. SRSF10 also represses inclusion of PGC1α exon 7a in hepatocytes, facilitating production of functional PGC1α protein that regulates glucose production. SRSF10-null mice exhibit defects in striated muscle development. Conditional KO mice, RNA-seq, minigene splicing assays, siRNA knockdown, glucose production assays Cell reports High 26586428
2016 In normally growing cells SRSF10 partially relieves repression of the Bcl-xS 5' splice site and interacts with both repressor hnRNP K and stimulatory hnRNP F/H on the Bcl-x pre-mRNA. Oxaliplatin-induced DNA damage (via ATM/CHK2) causes dephosphorylation of SRSF10, abrogates the interaction of SRSF10 with hnRNP F/H, and decreases association of SRSF10 and hnRNP K with the Bcl-x pre-mRNA, shifting splicing toward pro-apoptotic Bcl-xS. RNA immunoprecipitation, co-immunoprecipitation, siRNA knockdown, minigene splicing assays, ATM/CHK2 inhibition, RNA-seq Cell reports High 27851963
2017 Compound 1C8 promotes dephosphorylation of SRSF10 and increases its interaction with hTra2β. Depleting SRSF10 by RNAi reduces HIV-1 splicing and expression of Tat, Gag, and Env, mimicking 1C8's effect. 1C8 targets SRSF10-dependent splicing regulation rather than SRSF1. RNAi knockdown, immunoblotting for SRSF10 phosphorylation, co-immunoprecipitation, RT-PCR of HIV-1 splice variants Nucleic acids research Medium 27928057
2018 DNA damage reconfigures the assembly of splicing regulators on the Bcl-x pre-mRNA: SRSF10, 14-3-3ε, hnRNP A1/A2, and Sam68 collaborate to drive DNA-damage-induced shift toward pro-apoptotic Bcl-xS. RNA affinity assays identified 14-3-3ε and hnRNP A1 as proteins recovered with the SRSF10-binding region of Bcl-x transcript. RNA affinity pulldown, co-immunoprecipitation, siRNA knockdown, minigene splicing assays, RNA-seq Scientific reports Medium 29396485
2018 SRSF10 modulates alternative terminator usage of IL1RAP exon 13 to increase production of membrane form of IL1RAP (mIL1RAP). SRSF10 is transcriptionally upregulated by HPV E6/E7 via E2F1. The resulting mIL1RAP upregulates CD47 via NF-κB activation, inhibiting macrophage phagocytosis. Minigene splicing assays, siRNA knockdown, co-immunoprecipitation, ChIP, flow cytometry, phagocytosis assays Oncogene Medium 29429992
2020 SRSF10 binds to the SMN2 intronic splicing silencer ISS-N1 (identified by MS/MS and surface plasmon resonance imaging). The two isoforms of SRSF10 (differing in RS domain length) regulate SMN1 and SMN2 exon 7 inclusion with different strengths, correlating with RS domain length. Splice-switching oligonucleotides that shift the SRSF10 isoform ratio modulate endogenous SMN2 exon 7 inclusion. MS/MS proteomics on RNA affinity pulldown, surface plasmon resonance imaging, splice-switching oligonucleotides, RT-PCR Human mutation Medium 33300159
2020 SRSF10 acts as a restriction factor for HBV by regulating the level of nascent HBV RNA (not HBV RNA splicing). The dephosphorylated form of SRSF10 is likely responsible for its anti-HBV effect. SRSF10 was identified as a nuclear interactor of HBV core protein (HBc) by proteomic analysis of the HBc interactome in differentiated HepaRG cells. Affinity proteomics/mass spectrometry (HBc interactome), SRSF10 knockdown, pharmacological inhibition (1C8), quantitative RT-PCR for HBV RNA levels, nascent RNA analysis PLoS pathogens Medium 33180834
2020 SRSF10 binds a splicing regulatory cis-element in chicken ANP32A intron 4 (identified by RNA affinity purification/mass spectrometry and RIP), promoting production of the shorter ch-ANP32A-29 isoform at the expense of ch-ANP32A-33. Overexpression of SRSF10 reduces avian influenza virus polymerase activity and viral replication by decreasing the ch-ANP32A-33 isoform. RNA affinity purification and mass spectrometry, RIP, overexpression/knockdown, polymerase activity assays, viral replication assays Virus research Medium 32574681
2021 RNA immunoprecipitation confirmed that TTN-derived circular RNAs (cTTN1) bind SRSF10 via the back-splice junction motif. Loss of cTTN1 in iPSC-derived cardiomyocytes causes abnormal splicing of SRSF10 targets (MEF2A, CASQ2) and disrupts RBM20 localization, indicating that circRNA-mediated sequestration/presentation of SRSF10 modulates its splicing activity. RNA immunoprecipitation, shRNA-mediated selective knockdown of circRNA back-splice junction, engineered heart tissue contractility assays, splicing analysis by RT-PCR Circulation Medium 33583186
2021 SRSF10 downregulates the expression of IRF1 (a transcriptional activator of Act1) by being recruited to the lncRNA TRAF3IP2-AS1, thereby suppressing IL-17A signaling. Lentiviral overexpression of SRSF10 yields therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. Lentiviral overexpression, lncRNA-RBP interaction assays, IRF1 expression analysis, IL-17A signaling readouts, murine disease models Journal of immunology Low 33941656
2021 GPS167/192 compounds inhibit CLK1 and CLK4 kinases and increase their interaction with SRSF10, leading to impaired SRSF10 phosphorylation-dependent splicing activity (e.g., reduced BCLAF1-L production). GPS167 promotes p53-dependent apoptosis in CRC cells in a manner that requires both SRSF10 and p53. Co-immunoprecipitation (GPS167-induced SRSF10-CLK interaction), minigene splicing assays, siRNA knockdown, CRC cell growth/apoptosis assays, colonoid models NAR cancer Medium 34316707
2022 SRSF10 is essential for expansion of PLZF+ undifferentiated progenitor spermatogonia. SRSF10 directly binds thousands of spermatogonial mRNAs (iRIP-seq) and its depletion causes alternative splicing defects in genes involved in germ cell development (Nasp, Bclaf1, Rif1, Dazl, Kit, Ret, Sycp1), leading to failed spermatogonia differentiation and meiosis initiation. Germ cell-specific KO mice, bulk RNA-seq, single-cell RNA-seq, iRIP-seq (direct binding), immunostaining eLife High 36355419
2022 SRSF10 promotes exon 6 skipping of CDC25A pre-mRNA, producing a CDC25A(ΔE6) isoform that lacks two ubiquitination sites (Lys150, Lys169) and is therefore stabilized and retained in the nucleus. SRSF10 promotes Ser178 dephosphorylation of CDC25A to cause nuclear retention. CDC25A(ΔE6) is indispensable for SRSF10-driven HCC growth in vitro and in vivo. RNA sequencing, RIP and CLIP-qPCR, co-immunoprecipitation, immunofluorescence, mutagenesis of ubiquitination sites, xenograft models Journal of experimental & clinical cancer research Medium 36539837
2022 SRSF10 promotes inclusion of exon 10 in SREK1 (generating SREK1L), which in turn sustains expression of BLOC1S5-TXNDC5 (B-T) by inhibiting NMD. B-T functions as a ceRNA suppressing miR-30c-5p and miR-30e-5p, which further upregulates SRSF10 and TXNDC5, forming a positive SRSF10/SREK1L/B-T signaling loop in HCC. RNA splicing assays, siRNA knockdown, co-immunoprecipitation, luciferase reporter assays, HCC cell functional assays Nature communications Medium 35296659
2023 SRSF10 depletion in neural progenitor cells impairs NPC proliferation and cortical neurogenesis through modulation of the PI3K-AKT-mTOR-CCND2 pathway and through altered alternative splicing of Nasp (a cell cycle regulator isoform gene). Conditional KO mice, in utero electroporation, RNA-seq, RT-PCR of Nasp isoforms, pathway inhibitor experiments iScience Medium 37360696
2023 SRSF10 prevents exon 6 skipping of MDM4 pre-mRNA, thereby maintaining MDM4 protein levels that suppress p53, which in turn inhibits CD8+ T cell infiltration in HCC. SRSF10 also inhibits IFNα/γ signaling and promotes HIF1α-mediated PD-L1 upregulation. Hepatocyte-specific KO and OE mouse models, RNA-seq, co-immunoprecipitation, flow cytometry, CD8+ T cell depletion experiments, xenograft/orthotopic HCC models International immunopharmacology Medium 38113691
2024 SRSF10 interacts with the 3'-UTR of MYB mRNA to enhance MYB RNA stability, subsequently upregulating glycolysis-related enzymes (GLUT1, HK1, LDHA) and increasing lactate production. Elevated lactate promotes M2 macrophage polarization via histone H3K18 lactylation, creating an immunosuppressive tumor microenvironment. SRSF10/glycolysis/H3K18la forms a positive feedback loop. RNA immunoprecipitation (SRSF10-MYB 3'-UTR), co-culture systems, flow cytometry, ChIP for lactylation marks, tumor-bearing mouse models, patient-derived organotypic tumor spheroids Cancer communications Medium 39223929
2025 Casein kinase 1ε (CK1ε) directly interacts with SRSF10 and phosphorylates SRSF10 at S23 and S133, which is required for SRSF10 binding to Bcl-xL mRNA to favor Bcl-xL over Bcl-xS production. Overexpression of CK1ε abrogates the effect of SRSF10 knockdown on Bcl-xS/Bcl-xL ratio. Co-immunoprecipitation (CK1ε-SRSF10), in vitro kinase assay with phosphosite mapping (S23/S133), CK1δ/ε inhibitor SR3029, SRSF10 KD + CK1ε OE epistasis, xenograft model The Journal of biological chemistry Medium 40701249
2025 SRSF10 depletion in oligodendrocyte lineage cells (OLCs) causes hypomyelination and reduced OLC numbers during mouse CNS development by impairing early OLC differentiation (not proliferation or apoptosis). Among SRSF10-regulated AS targets, correcting the alternative splicing of Myo5a using antisense oligonucleotides reverses OLC differentiation inhibition caused by SRSF10 depletion. OLC-specific conditional KO mice, RNA-seq, RIP-seq (direct binding), antisense oligonucleotide rescue of Myo5a splicing Nucleic acids research High 40439883
2026 SRSF10 promotes inclusion of exon 2 in BCAT2 mRNA, activating mTOR signaling. SRSF10 blockade (by inhibitor 1C8) reprograms tumor-associated macrophages via CCL2, enhancing CD8+ T-cell infiltration and potentiating anti-PD-1 efficacy in gastric cancer models. Multiple mouse GC models, RNA splicing analysis, SRSF10 knockout/inhibitor experiments, flow cytometry, mTOR pathway analysis, orthotopic model with PD-1 antibody combination Cell death & disease Medium 42020371
2026 SRSF10 induces retention of BIN1 exon 12, producing a BIN1(12+) isoform that directly interacts with and activates ANXA1, contributing to cisplatin resistance in bladder cancer. This was shown by co-immunoprecipitation confirming BIN1(12+)-ANXA1 interaction and by functional rescue experiments. SRSF10 KD/OE, RNA sequencing, RIP-qPCR/CLIP, co-immunoprecipitation (BIN1(12+)-ANXA1), xenograft model, cisplatin IC50 assays Oncogene Medium 41942629
2025 SRSF10 preferentially binds and traffics mRNAs to the central axon of dorsal root ganglion neurons, establishing compartment-specific translational programs in sensory neurons. Translating Ribosome Affinity Purification (TRAP) with spatial compartment-specific sequencing, cross-dataset integration with scRNA-seq, RBP-mRNA binding analysis bioRxivpreprint Low
2007 TASR-1 (SRSF10), but not TASR-2, influences alternative splicing of type II and type XI collagen genes in mouse ATDC5 chondroprogenitor cells. TASR-1 can also down-regulate expression of type X collagen. Retroviral stable expression in ATDC5 cells, RT-PCR for collagen isoforms, microarray analysis Biochemical and biophysical research communications Low 17367759

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 187 14765198
2002 The SR protein SRp38 represses splicing in M phase cells. Cell 167 12419250
2014 BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells. Nature communications 152 25091051
2024 Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma. Cancer communications (London, England) 135 39223929
2018 SRSF10-mediated IL1RAP alternative splicing regulates cervical cancer oncogenesis via mIL1RAP-NF-κB-CD47 axis. Oncogene 101 29429992
2007 A complex signaling pathway regulates SRp38 phosphorylation and pre-mRNA splicing in response to heat shock. Molecular cell 97 17936706
2009 SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart. Developmental cell 86 19386262
2014 Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation. Nucleic acids research 83 24442672
2008 Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. Nature structural & molecular biology 81 18794844
2016 SRSF10 Connects DNA Damage to the Alternative Splicing of Transcripts Encoding Apoptosis, Cell-Cycle Control, and DNA Repair Factors. Cell reports 61 27851963
2020 SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway. Journal of experimental & clinical cancer research : CR 58 32600379
2014 SRSF10 regulates alternative splicing and is required for adipocyte differentiation. Molecular and cellular biology 49 24710272
2015 SRSF10 Plays a Role in Myoblast Differentiation and Glucose Production via Regulation of Alternative Splicing. Cell reports 42 26586428
2017 Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication. Nucleic acids research 41 27928057
2020 Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production. PLoS pathogens 40 33180834
2022 The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma. Nature communications 36 35296659
2018 hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage. Scientific reports 33 29396485
2005 Hsp27 enhances recovery of splicing as well as rephosphorylation of SRp38 after heat shock. Molecular biology of the cell 33 16339078
2021 SRSF10: an atypical splicing regulator with critical roles in stress response, organ development, and viral replication. RNA (New York, N.Y.) 30 34315816
2005 Multiple properties of the splicing repressor SRp38 distinguish it from typical SR proteins. Molecular and cellular biology 29 16135820
2021 Titin Circular RNAs Create a Back-Splice Motif Essential for SRSF10 Splicing. Circulation 28 33583186
2021 Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases. Journal of immunology (Baltimore, Md. : 1950) 27 33941656
2022 SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing. eLife 26 36355419
2022 SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis. Journal of experimental & clinical cancer research : CR 25 36539837
2021 A novel class of inhibitors that target SRSF10 and promote p53-mediated cytotoxicity on human colorectal cancer cells. NAR cancer 23 34316707
2005 Inhibition of neurogenesis by SRp38, a neuroD-regulated RNA-binding protein. Development (Cambridge, England) 21 15728676
2023 lncR-GAS5 upregulates the splicing factor SRSF10 to impair endothelial autophagy, leading to atherogenesis. Frontiers of medicine 15 36645633
2021 ERK1/2-EGR1-SRSF10 Axis Mediated Alternative Splicing Plays a Critical Role in Head and Neck Cancer. Frontiers in cell and developmental biology 15 34616729
2010 Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27. Molecular and cellular biology 15 21135127
2023 SRSF10 facilitates HCC growth and metastasis by suppressing CD8+T cell infiltration and targeting SRSF10 enhances anti-PD-L1 therapy. International immunopharmacology 14 38113691
2020 Identification of SRSF10 as a regulator of SMN2 ISS-N1. Human mutation 14 33300159
2023 Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery. Journal of translational medicine 11 38049848
2023 SRSF10 regulates proliferation of neural progenitor cells and affects neurogenesis in developing mouse neocortex. iScience 9 37360696
2020 SRSF10 inhibits the polymerase activity and replication of avian influenza virus by regulating the alternative splicing of chicken ANP32A. Virus research 8 32574681
2024 High Expression of SRSF10 Promotes Colorectal Cancer Progression by Aberrant Alternative Splicing of RFC5. Technology in cancer research & treatment 6 39110418
2025 SRSF10 regulates oligodendrocyte differentiation during mouse central nervous system development by modulating pre-mRNA splicing. Nucleic acids research 5 40439883
2007 TASR-1 regulates alternative splicing of collagen genes in chondrogenic cells. Biochemical and biophysical research communications 5 17367759
2025 ALKBH5-mediated m6A regulates the alternative splicing events of SRSF10 in ovarian cancer. Cancer gene therapy 4 40175608
2022 A novel biomarker NIFK-AS1 promotes hepatocellular carcinoma cell cycle progression through interaction with SRSF10. Journal of gastrointestinal oncology 4 36092356
2014 Genome-wide analysis of SRSF10-regulated alternative splicing by deep sequencing of chicken transcriptome. Genomics data 3 26484059
2025 SRSF10 regulates isoform expression of transcripts associated with proliferative diabetes retinopathy in ARPE-19 cells based on long-read RNA and immunoprecipitation sequencing. Gene 1 40090530
2025 CK1ε/SRSF10 axis regulates the alternative splicing of Bcl-x in lung cancer cells. The Journal of biological chemistry 1 40701249
2024 SRSF10 regulates migration of neural progenitor cells and granule cells and affects the formation of dentate gyrus during the development of mouse hippocampus. Neuroscience 1 38960088
2026 SRSF10 promotes cisplatin resistance in bladder cancer via BIN1 Exon 12 retention and ANXA1 activation. Oncogene 0 41942629
2026 Disrupting SRSF10-dependent BCAT2 exon skipping reprograms tumor-associated macrophages and enhances anti-PD-1 efficacy in gastric cancer. Cell death & disease 0 42020371
2025 SNORD46 stabilized by SRSF10 regulating lipid metabolism and cell proliferation of glioma cells via mediating FOXO4 2'-O-methylation. Cellular signalling 0 40681010
2025 LncRNA PSMA-AS1 affects glioma cell metastasis through mediating pyroptosis via miR-140-3p/SRSF10 axis. Cytotechnology 0 41018137

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