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SRSF11

Serine/arginine-rich splicing factor 11 · UniProt Q05519

Length
484 aa
Mass
53.5 kDa
Annotated
2026-06-10
10 papers in source corpus 7 papers cited in narrative 7 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRSF11 is a nuclear speckle-localized SR-family splicing factor that regulates alternative pre-mRNA splicing and transcript stability across multiple cellular programs by directly binding exonic and 3' UTR RNA elements (PMID:16943417, PMID:26286192, PMID:36394206). As a splicing regulator it binds a purine-rich element in tau exon 10 to repress its inclusion, antagonizing the activating SR protein Tra2beta (PMID:16943417), and it directs additional exon-inclusion/retention decisions including HSPA12A exon 2 retention and RAD52 exon 10 inclusion (PMID:36394206, PMID:41198615). Beyond splicing, SRSF11 binds the LRP8 3' UTR and the third exon of apoE mRNA to stabilize these transcripts, restraining JNK signaling and supporting cognitive function in vivo (PMID:31269452). Its localization to nuclear speckles underlies an S-phase function in which SRSF11 binds the telomerase RNA TERC and the telomeric protein TRF2 to recruit active telomerase to telomeres and enable telomere elongation (PMID:26286192). SRSF11 activity is set by post-translational modification: PAK5 phosphorylates it at Ser287 to protect it from ubiquitin-mediated degradation (PMID:36394206), and KAT2A succinylates it at Lys419 to strengthen its spliceosome interactions (PMID:41198615). Through these activities SRSF11 has been linked to colorectal cancer metastasis and hepatocellular carcinoma radioresistance (PMID:36394206, PMID:41198615).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2006 High

    Established SRSF11 as a sequence-specific alternative splicing regulator by showing it represses tau exon 10 inclusion through a defined exonic element, defining its core molecular activity.

    Evidence GFP exon-skipping reporter, expression cloning, RNAi knockdown, deletion mutagenesis of the exonic purine-rich element, and antagonism assay with Tra2beta

    PMID:16943417

    Open questions at the time
    • Direct RNA binding shown functionally but not by biochemical footprinting
    • No structural basis for SRSF11–Tra2beta antagonism
    • Generality to other targets not addressed in this study
  2. 2015 High

    Revealed a splicing-independent role: SRSF11 uses its nuclear speckle localization to recruit telomerase to telomeres, answering how telomerase reaches its substrate during S phase.

    Evidence Reciprocal Co-IP of SRSF11 with TERC and TRF2, immunofluorescence localization, S-phase cell-cycle analysis, and SRSF11 depletion with telomere elongation readout

    PMID:26286192

    Open questions at the time
    • Whether TERC/TRF2 binding is direct RNA/protein contact or speckle-mediated not fully resolved
    • Domain of SRSF11 mediating recruitment unmapped
    • Link between its splicing activity and telomerase function unclear
  3. 2019 High

    Extended SRSF11 function to mRNA stabilization, showing it stabilizes LRP8 and apoE transcripts to restrain JNK signaling and preserve cognition, separating its stabilizer role from splicing.

    Evidence RIP for direct mRNA binding, mRNA stability assays, genetic rescue with LRP8/apoE restoration, JNK readout, and prefrontal cortex knockdown in mice with behavioral tests

    PMID:31269452

    Open questions at the time
    • Mechanism by which binding stabilizes transcripts unknown
    • RNA element required for binding not mapped
    • Relationship to its splicing activity not addressed
  4. 2022 High

    Connected SRSF11 to cancer and to upstream regulation, showing direct HSPA12A binding drives exon retention promoting metastasis and that PAK5 phosphorylation at S287 controls SRSF11 protein stability.

    Evidence In vivo UV-CLIP, minigene reporter, Co-IP, phospho-tag SDS-PAGE, in vitro PAK5 kinase assay, RNA-seq, and in vitro/in vivo metastasis models

    PMID:36394206

    Open questions at the time
    • E3 ligase mediating SRSF11 degradation not identified
    • Whether S287 phosphorylation alters RNA binding not tested
    • Breadth of PAK5-dependent splicing changes unquantified
  5. 2025 Medium

    Identified a second PTM controlling SRSF11, showing KAT2A-mediated K419 succinylation stabilizes spliceosome interactions and promotes RAD52 exon 10 inclusion to drive HR repair and radioresistance.

    Evidence Co-IP for KAT2A–SRSF11 interaction, succinylation site mapping, pre-mRNA binding and exon inclusion assays, and KAT2A–SRSF11 disruption with radiation sensitivity readout in HCC models

    PMID:41198615

    Open questions at the time
    • Single study without independent replication
    • Structural effect of K419 succinylation on spliceosome contacts not resolved
    • Interplay between succinylation and S287 phosphorylation unexplored
  6. 2025 Medium

    Placed SRSF11 downstream of exosomal miRNA control, showing miR-126-5p inhibits SRSF11 and that SRSF11 binds Sirt1 and P21 pre-mRNAs to regulate senescence-associated isoforms.

    Evidence RIP confirming SRSF11–Sirt1/P21 pre-mRNA binding, exosome isolation, miRNA target validation, senescence assays, and an in vivo DVT mouse model

    PMID:41343940

    Open questions at the time
    • Single-lab study
    • Splicing outcomes on Sirt1/P21 only partially characterized
    • Direct vs indirect regulation of isoform choice not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SRSF11's distinct activities — splicing repression/activation, mRNA stabilization, and telomerase recruitment — are coordinated within one protein and selectively deployed across contexts remains unresolved.
  • No structural model linking RNA-binding to its multiple functions
  • Determinants of target selectivity unknown
  • Integration of competing PTMs (S287 phosphorylation, K419 succinylation) not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1643685 Disease 2
Complex memberships
spliceosome

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 SRp54/SFRS11 (SRSF11) acts as a repressor of tau exon 10 inclusion: overexpression suppresses exon 10 inclusion, siRNA knockdown increases it. SRSF11 binds a purine-rich element in tau exon 10 and antagonizes Tra2beta, an SR-domain protein that promotes exon 10 inclusion. Deletion of the exonic purine-rich element abolishes SRSF11 repressor activity. GFP-based exon-skipping reporter assay, expression cloning, RNA interference knockdown, deletion mutagenesis of exonic element, functional antagonism assay with Tra2beta Molecular and cellular biology High 16943417
2015 SRSF11 localizes to nuclear speckles and functions as a nuclear speckle-targeting factor for telomerase. It binds TERC (telomerase RNA component) directly and also binds TRF2 at telomeres. During S phase, SRSF11 directs active telomerase to nuclear speckles; a subset of telomeres resides constitutively at nuclear speckles. Depletion of SRSF11 prevents telomerase association with nuclear speckles, disrupts telomerase recruitment to telomeres, and abrogates telomere elongation. Co-immunoprecipitation (SRSF11 with TERC and TRF2), subcellular fractionation/immunofluorescence showing nuclear speckle localization, cell-cycle-specific analysis (S-phase), SRSF11 depletion with telomere elongation readout Nucleic acids research High 26286192
2019 SRSF11 directly binds the 3' UTR of LRP8 mRNA and the third exon of apoE mRNA, stabilizing both transcripts. Loss of SFRS11/SRSF11 reduces LRP8 and apoE levels, leading to activation of JNK signaling. Restoration of LRP8 and apoE reduces JNK signaling elevated in SFRS11-deficient cells and rescues aging-like cognitive phenotypes. RNA immunoprecipitation (RIP) to confirm direct mRNA binding, mRNA stability assays, genetic rescue experiments (LRP8/apoE restoration in SFRS11-deficient cells), JNK signaling readout, prefrontal cortex-specific knockdown in mice with cognitive behavioral tests Cell reports High 31269452
2022 SRSF11 promotes colorectal cancer metastasis by directly binding a motif in exon 2 of HSPA12A pre-mRNA (identified by UV-CLIP and minigene reporter), causing exon 2 retention and increased HSPA12A transcript stability, which in turn elevates N-cadherin expression. The oncogenic kinase PAK5 phosphorylates SRSF11 at serine 287, protecting it from ubiquitin-mediated degradation. In vivo UV crosslinking and immunoprecipitation (CLIP), minigene reporter assay, Co-immunoprecipitation, Phospho-tag SDS-PAGE, in vitro kinase assay (PAK5 phosphorylating SRSF11 at S287), RNA-seq for AS events, in vitro and in vivo metastasis models Clinical and translational medicine High 36394206
2025 KAT2A directly interacts with SRSF11 and catalyzes succinylation of SRSF11 at lysine 419 (K419). K419 succinylation stabilizes SRSF11-spliceosome interactions and promotes inclusion of exon 10 of RAD52 pre-mRNA, preserving the RAD51-binding domain of RAD52. This facilitates RAD52-RAD51 dimer assembly and homologous recombination repair, leading to radioresistance in hepatocellular carcinoma. Co-immunoprecipitation (KAT2A-SRSF11 interaction), structural and functional analyses of K419 succinylation, pre-mRNA binding assays, exon inclusion assays (RAD52 exon 10), in vitro and in vivo HCC models, genetic disruption of KAT2A-SRSF11 axis with radiation sensitivity readout Signal transduction and targeted therapy Medium 41198615
2025 miR-126-5p delivered by M1 macrophage exosomes targets and inhibits SRSF11 expression. SRSF11 binds Sirt1 and P21 precursor mRNAs (confirmed by RIP), and its inhibition leads to dysregulation of alternative splicing of these genes with an increase in pro-senescence isoforms, driving endothelial cell senescence. RIP experiments confirming SRSF11 binding to Sirt1/P21 pre-mRNA, exosome isolation and characterization, luciferase/miRNA target validation, SA-β-gal staining and flow cytometry for senescence, in vivo DVT mouse model International immunopharmacology Medium 41343940
2025 SRSF11 and SRRM1 share common protein interactors and RNA targets and together promote oncogenic NUMB exon 9 (E9) splicing in colorectal, lung, and breast cancer cell lines, identified in a genome-wide CRISPR screen using a NUMB E9 splicing reporter. Genome-wide CRISPR screen with NUMB exon 9 splicing reporter, protein interaction studies, RNA target analysis bioRxivpreprint Low bio_10.1101_2025.08.20.671097

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 SRp54 (SFRS11), a regulator for tau exon 10 alternative splicing identified by an expression cloning strategy. Molecular and cellular biology 50 16943417
2005 [99mTcOAADT]-(CH2)2-NEt2: a potential small-molecule single-photon emission computed tomography probe for imaging metastatic melanoma. Cancer research 29 15958536
2019 SFRS11 Loss Leads to Aging-Associated Cognitive Decline by Modulating LRP8 and ApoE. Cell reports 27 31269452
2015 Involvement of SRSF11 in cell cycle-specific recruitment of telomerase to telomeres at nuclear speckles. Nucleic acids research 21 26286192
2022 Alternative splicing of HSPA12A pre-RNA by SRSF11 contributes to metastasis potential of colorectal cancer. Clinical and translational medicine 19 36394206
2012 Application of real-time PCR-based SNP detection for mapping of Net2, a causal D-genome gene for hybrid necrosis in interspecific crosses between tetraploid wheat and Aegilops tauschii. Genes & genetic systems 12 22820387
2016 Fine mapping and genetic association analysis of Net2, the causative D-genome locus of low temperature-induced hybrid necrosis in interspecific crosses between tetraploid wheat and Aegilops tauschii. Genetica 10 27502693
2025 KAT2A-driven succinylation of SRSF11 enforces spliceosome-mediated RAD52 splicing to promote homologous recombination and radioresistance in hepatocellular carcinoma. Signal transduction and targeted therapy 2 41198615
2025 M1 macrophage-derived exosomal miR-126-5p promotes endothelial cell senescence and deep vein thrombosis by targeting splicing factor SRSF11. International immunopharmacology 1 41343940
2026 Dysregulation of SRSF11 in Cancer: Mechanistic Insights and Biomarker Potential for Diagnosis and Therapy. Journal of Cancer 0 41584036

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