Affinage

SRSF3

Serine/arginine-rich splicing factor 3 · UniProt P84103

Length
164 aa
Mass
19.3 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRSF3 (SRp20) is a multifunctional SR family splicing factor that orchestrates gene expression at multiple post-transcriptional levels — pre-mRNA splicing, alternative polyadenylation, mRNA export, pri-miRNA processing, and translational control — and is essential for early embryonic development and tissue homeostasis. Its RRM domain preferentially recognizes C-rich RNA sequences (CAUC/CNNC motifs), while an adjacent arginine-rich peptide mediates direct interaction with the export receptor TAP/NXF1 to facilitate nucleocytoplasmic mRNA export, a function required in megakaryocytes for platelet RNA loading and in hepatocytes for metabolic gene expression (PMID:17036044, PMID:34852174, PMID:23299886). SRSF3 autoregulates its own expression by promoting inclusion of a poison exon 4 — a circuit modulated by PTBP1/2 — and controls alternative splicing of diverse targets including p53β, insulin receptor, mTOR, PKM, and caspase-2, while also recruiting DROSHA to CNNC motifs at pri-miRNA basal junctions to enhance Microprocessor cleavage (PMID:9305649, PMID:26416554, PMID:22777358, PMID:29615481). Its activity is regulated post-translationally by Akt-mediated phosphorylation driving nuclear translocation, PPM1G-mediated dephosphorylation, and neddylation at K11 triggering proteasomal degradation, while Aurora B-dependent histone H3S10 phosphorylation controls its release from mitotic chromatin (PMID:34184034, PMID:31393851, PMID:19250906).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing that SRSF3 autoregulates its own splicing resolved how SR protein levels are homeostatically controlled: SRSF3 overexpression activates inclusion of its exon 4, producing a truncated non-functional isoform, while ASF/SF2 antagonizes this effect.

    Evidence Reporter minigene transfection and overexpression in mammalian cells

    PMID:9305649

    Open questions at the time
    • Endogenous binding sites on exon 4 were not mapped
    • Trans-acting factors beyond ASF/SF2 that modulate the autoregulatory loop were unknown
  2. 1998 High

    Demonstrating that SRSF3 regulates alternative polyadenylation — not just splicing — via its RRM domain expanded its functional repertoire beyond exon selection: an RRM-only mutant acted as dominant negative by blocking CstF access to the calcitonin/CGRP alternative poly(A) site.

    Evidence Dominant-negative mutant overexpression with polyadenylation factor binding assays

    PMID:9710581

    Open questions at the time
    • Whether SRSF3 directly competes with CstF for RNA binding or acts indirectly was unresolved
    • Genome-wide scope of APA regulation by SRSF3 was unknown
  3. 1999 High

    SELEX-based identification of the SRSF3 RRM binding motif (A/U)C(A/U)(A/U)C provided the first sequence-level understanding of how SRSF3 selects its RNA targets, and genetic knockout showed the protein is non-redundantly essential for blastocyst formation.

    Evidence In vitro SELEX with recombinant RRM; Cre-loxP knockout mouse embryo analysis

    PMID:10094314 PMID:10469594

    Open questions at the time
    • In vivo binding sites remained unmapped
    • Mechanism of morula-stage lethality was not elucidated
  4. 2001 High

    Showing that SRSF3 promotes nucleocytoplasmic export of intronless mRNAs via a specific 22-nt RNA element established a non-splicing nuclear function: SRSF3 shuttles between nucleus and cytoplasm and directly facilitates mRNA export.

    Evidence UV cross-linking, Xenopus oocyte microinjection, antibody inhibition in HeLa cells

    PMID:11336712

    Open questions at the time
    • The export receptor partner was not yet identified
    • Whether SRSF3 accompanies mRNA to the cytoplasm or is recycled at the pore was unclear
  5. 2006 High

    NMR structure determination of the SRSF3 RRM–CAUC complex and identification of the TAP/NXF1-binding arginine-rich peptide resolved how a single SR protein couples RNA recognition to mRNA export at atomic resolution, and separately, RNA Pol II CTD was shown to recruit SRSF3 for exon-skipping decisions.

    Evidence NMR structure determination, mutagenesis, RNA-protein binding assays; alpha-amanitin-resistant Pol II CTD mutants with fibronectin reporter

    PMID:17028590 PMID:17036044

    Open questions at the time
    • Full-length SRSF3 structure including the RS domain was not determined
    • How phosphorylation state modulates TAP interaction was unknown
  6. 2008 High

    Multiple studies revealed SRSF3 as a versatile splicing regulator of endogenous and viral targets — insulin receptor exon 11 (antagonized by CUG-BP1), papillomavirus early-to-late splice switch, and CD44 downstream of Wnt/β-catenin transcriptional activation of SRSF3 — establishing context-dependent exon inclusion or skipping.

    Evidence RNA affinity chromatography and minigene assays (insulin receptor); raft cultures and splicing assays (HPV); promoter reporter and dominant-negative TCF4 (CD44/Wnt)

    PMID:18945760 PMID:18952824 PMID:19047369

    Open questions at the time
    • Genome-wide target inventory was still lacking
    • Position-dependent rules for SRSF3 promoting inclusion vs. skipping were not systematically defined
  7. 2009 High

    Discovery that Aurora B kinase-mediated H3S10 phosphorylation evicts SRSF3 from mitotic chromatin linked chromatin modifications to SR protein dynamics, revealing an epigenetic control layer for splicing factor availability.

    Evidence ChIP, Aurora B inhibition, siRNA knockdown, immunofluorescence

    PMID:19250906

    Open questions at the time
    • Whether H3S10ph directly disrupts SRSF3–chromatin contacts or acts through an intermediary was unresolved
    • Functional consequences for co-transcriptional splicing during mitotic exit were not tested
  8. 2012 High

    Identification of SRSF3 as a direct regulator of p53β alternative splicing — where SRSF3 suppresses inclusion of the β-specific exon — connected SRSF3 to the senescence and tumor suppressor pathway.

    Evidence CLIP, RNA pulldown, siRNA knockdown, TP53 minigene splicing assay

    PMID:22777358

    Open questions at the time
    • Whether SRSF3 regulates other p53 isoforms was not examined
    • In vivo relevance in tumor models was not established
  9. 2013 High

    Hepatocyte-specific Srsf3 knockout revealed that SRSF3 controls metabolic homeostasis by ensuring correct splicing of key glucose and lipid metabolism regulators (Hnf1α, Ern1, Hmgcs1), and separately, cytoplasmic SRSF3 was shown to repress translation of PDCD4 mRNA through 5'-UTR binding and P-body localization.

    Evidence Conditional hepatocyte KO mouse with RNA splicing analysis; polysome profiling and live-cell imaging in cell lines

    PMID:23299886 PMID:24292556

    Open questions at the time
    • Direct binding sites on metabolic target pre-mRNAs in hepatocytes were not mapped by CLIP
    • How SRSF3 is recruited to P-bodies was unknown
  10. 2015 Medium

    PTBP1/PTBP2 were identified as trans-acting suppressors of SRSF3 exon 4 inclusion, completing the autoregulatory circuit: PTBP1/2 bind an exonic splicing suppressor in exon 4 to prevent its inclusion, causing SRSF3 overexpression in cancer, while SRSF3 reciprocally promotes PTBP2 expression.

    Evidence RNA binding assays, overexpression/knockdown, RT-PCR splicing analysis

    PMID:26416554

    Open questions at the time
    • Structural basis of PTBP binding to exon 4 was not resolved
    • In vivo validation of the SRSF3-PTBP circuit in tumors was lacking
  11. 2018 High

    Multiple lines of evidence expanded SRSF3's functional scope: it recruits DROSHA to pri-miRNA CNNC motifs to enhance Microprocessor cleavage; it maintains transcriptome integrity in oocytes by repressing B2 SINE elements; it cooperates with PTBP1/hnRNPA1 to control PKM splicing and glycolytic metabolism; and it interacts with the NEXT/RNA exosome complex for intronless mRNA degradation.

    Evidence In vitro pri-miRNA processing and mutagenesis; oocyte-specific KO with scRNA-seq; RIP/IP with metabolic assays; Co-IP and mRNA stability assays

    PMID:29615481 PMID:29928511 PMID:30150655 PMID:30279379

    Open questions at the time
    • Whether DROSHA recruitment requires SRSF3 phosphorylation was untested
    • Mechanism of B2 SINE repression by SRSF3 was not molecularly defined
    • NEXT complex interaction awaits structural characterization
  12. 2019 High

    Neddylation at K11 was identified as a specific degradation signal for SRSF3 under lipotoxic stress, and cardiomyocyte-specific KO revealed that SRSF3 controls mTOR splicing to maintain translational homeostasis in the heart — its loss causing lethal systolic dysfunction within days.

    Evidence K11R mutagenesis with neddylation/proteasome assays in hepatocytes and in vivo; inducible cardiomyocyte KO mouse with RNA-seq and mTOR activity assays

    PMID:31145021 PMID:31393851

    Open questions at the time
    • The E3 ligase mediating SRSF3 neddylation was not identified
    • Whether neddylation-mediated degradation occurs in cardiomyocytes was not tested
  13. 2021 High

    Transcriptome-wide iCLIP and 3'-end sequencing showed SRSF3 promotes distal polyadenylation site usage by binding upstream of proximal poly(A) sites and by maintaining CFIm levels through splicing, while Akt-mediated phosphorylation downstream of PDGFRα was shown to drive SRSF3 nuclear translocation essential for craniofacial development.

    Evidence iCLIP/3'-end sequencing with SRSF3/SRSF7 knockdown and domain swaps; phosphorylation assays and neural crest-specific conditional KO mouse

    PMID:33706811 PMID:34184034

    Open questions at the time
    • Whether Akt directly phosphorylates the RS domain or acts through intermediate kinases was not definitively resolved
    • Structural basis for SRSF3 competition with SRSF7 at poly(A) sites was not determined
  14. 2022 High

    Megakaryocyte-specific Srsf3 KO causing macrothrombocytopenia demonstrated that SRSF3-mediated mRNA export is essential for platelet biogenesis — RNA fails to transit to the cytoplasm and load into platelets — while SRSF3 was also found in a hnRNPH1/PTBP2 complex regulating meiotic splicing in spermatocytes.

    Evidence Megakaryocyte-specific conditional KO with mRNA localization assays; hnRNPH1 KO with Co-IP and RNA-seq in germ cells

    PMID:34852174 PMID:35739118

    Open questions at the time
    • Which specific mRNAs require SRSF3 for export in megakaryocytes versus hepatocytes was not compared
    • Whether SRSF3 has a direct splicing role in spermatogenesis independent of hnRNPH1 was not tested
  15. 2023 High

    High-throughput pri-miRNA cleavage assays confirmed that SRSF3 stimulates Microprocessor through CNNC motif secondary structures, and hepatocyte SRSF3 loss was linked to impaired lipophagy through increased ubiquitination and degradation of the SNARE protein STX17.

    Evidence Systematic in vitro Microprocessor cleavage with mutagenesis; hepatocyte SRSF3 KO with ubiquitination and autophagy flux assays

    PMID:36750366 PMID:36764525

    Open questions at the time
    • Whether SRSF3 regulates STX17 through direct splicing control or an indirect pathway was not fully delineated
    • Structural basis for CNNC secondary structure recognition by SRSF3 was not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length atomic structure of SRSF3 with its RS domain, the complete set of rules governing position-dependent splicing activation versus repression, the identity of the E3 ligase for K11 neddylation, and how SRSF3's multiple cytoplasmic functions (translation repression, P-body localization, IRES-mediated translation) are coordinated with its nuclear roles.
  • No full-length structural model exists
  • Comprehensive position-dependent splicing code not established
  • Neddylation E3 ligase unknown
  • Cytoplasmic vs. nuclear function partitioning mechanism uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0140110 transcription regulator activity 7 GO:0045182 translation regulator activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2 GO:0005694 chromosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-9609507 Protein localization 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
DROSHAHNRNPA1HNRNPH1NXF1PPM1GPTBP1PTBP2TARDBP
Complex memberships
Microprocessor (DROSHA recruitment)NEXT/RNA exosome complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SRp20 (SRSF3) interacts specifically with a 22-nt RNA element from the histone H2a gene to promote nucleocytoplasmic export of intronless mRNAs in mammalian cells and Xenopus oocytes; antibodies to SRp20 eliminate RNA binding and inhibit export, and SRp20 can be UV cross-linked to polyadenylated RNA in both nucleus and cytoplasm of HeLa cells. UV cross-linking, transient transfection, Xenopus oocyte microinjection, antibody inhibition Molecular cell High 11336712
1997 SRp20 (SRSF3) regulates alternative splicing of its own pre-mRNA in an autoregulatory manner: overexpression of SRp20 activates inclusion of its alternative exon 4 (encoding a truncated protein lacking the RS domain), while ASF/SF2 antagonizes this effect by suppressing exon 4 recognition. Reporter gene constructs, transient transfection, overexpression The EMBO journal High 9305649
1999 SELEX analysis demonstrates that the RRM of SRp20 (SRSF3) selects RNA sequences centered around an (A/U)C(A/U)(A/U)C motif, and SRp20 can act as a splicing transactivator through its specific RNA targets; 9G8 uses a zinc knuckle in addition to its RRM to define its distinct binding specificity. SELEX, UV cross-linking, immunoprecipitation, S100 complementation splicing assay with recombinant proteins RNA (New York, N.Y.) High 10094314
1998 SRp20 (SRSF3) promotes alternative 3'-terminal exon inclusion in the calcitonin/CGRP gene via recognition of an intronic enhancer element; a mutant SRp20 containing only the RRM (lacking the RS domain) acts as a dominant negative that inhibits binding of polyadenylation factor CstF to the alternative poly(A) site, demonstrating SRp20 can regulate alternative polyadenylation. Transient transfection, mutant protein overexpression, polyadenylation factor binding assay Molecular and cellular biology High 9710581
2006 The RNA polymerase II CTD is required for the inhibitory action of SRp20 on fibronectin cassette exon inclusion; the CTD promotes exon skipping by recruiting SRp20, and this effect is independent of transcription elongation rate. Alpha-amanitin-resistant pol II CTD mutants, fibronectin reporter minigenes, transfection Nature structural & molecular biology High 17028590
2006 NMR solution structures of the SRp20 RRM and of the SRp20 RRM in complex with RNA 5'-CAUC-3' reveal that all 4 nucleotides are contacted but the 5' cytosine is primarily specifically recognized. A short arginine-rich peptide adjacent to the RRM of SRp20 and 9G8, which does not contact RNA, is necessary and sufficient for interaction with the mRNA export factor TAP/NXF1. NMR structure determination, RNA-protein binding assays, mutagenesis The EMBO journal High 17036044
1999 Cre-loxP-mediated knockout of SRp20 (SRSF3) in mice is lethal; mutant embryos fail to form blastocysts and die at the morula stage, demonstrating a non-redundant essential function for SRSF3 in early development. Conditional knockout (Cre-loxP), immunofluorescence staining Current biology : CB High 10469594
2009 SRp20 (SRSF3) associates with interphase chromatin and is released from hyperphosphorylated mitotic chromosomes; this dissociation is regulated by Aurora B kinase-mediated histone H3 serine 10 phosphorylation, as inhibition of Aurora B increases SRp20 retention on mitotic chromosomes. ChIP, siRNA knockdown, Aurora B kinase inhibition, immunofluorescence Molecular cell High 19250906
2012 SRSF3 binds to an alternatively spliced exon uniquely included in p53β mRNA through SRSF3 consensus binding sequences (demonstrated by RNA pulldown and CLIP assays), and functions to inhibit inclusion of the p53β-specific exon; downregulation of SRSF3 promotes p53β production, leading to cellular senescence. RNA pulldown, CLIP, siRNA knockdown, TP53 minigene splicing assay Oncogene High 22777358
2013 Hepatocyte-specific deletion of Srsf3 in mice causes disrupted hepatic architecture and impaired hepatocyte maturation with alterations in glucose and lipid homeostasis; SRSF3 loss causes aberrant splicing of Hnf1α, Ern1, Hmgcs1, Dhcr7, and Scap, which are critical regulators of glucose and lipid metabolism. Conditional knockout mouse, RNA splicing analysis, phenotypic characterization Nature communications High 23299886
2013 SRSF3 represses translation of PDCD4 mRNA by associating with its 5'-UTR; SRSF3 silencing shifts PDCD4 mRNA into translating polysome fractions, SRSF3 overexpression shifts it to non-translating fractions, and SRSF3 co-localizes with PDCD4 mRNA in P-bodies in live cells. Polysome profiling, live cell imaging, reporter assays, RNA immunoprecipitation Cell death and differentiation High 24292556
2018 SRSF3 recruits DROSHA to the basal junction of primary microRNAs (pri-miRNAs) in a CNNC motif-dependent manner (located ~17 nt from the Microprocessor cleavage site), thereby enhancing Microprocessor activity and pri-miRNA processing. In vitro pri-miRNA processing assays, mutagenesis of CNNC motifs, functional complementation RNA (New York, N.Y.) High 29615481
2008 SRp20 (SRSF3) controls the papillomavirus early-to-late switch by binding to A/C-rich RNA elements (SE4 element), suppressing selection of a late-specific splice site; SRp20 levels inversely correlate with late L1 capsid protein expression in differentiating keratinocytes. RNA-protein interaction assays, raft culture, knockdown/overexpression, splicing assays Journal of virology High 18945760
2008 SRp20 (SRSF3) and CUG-BP1 act antagonistically to regulate insulin receptor exon 11 alternative splicing: SRp20 binds exonic splicing enhancers identified by RNA affinity chromatography and promotes exon 11 inclusion, while CUG-BP1 binds exonic and intronic silencer elements to promote skipping. RNA affinity chromatography, overexpression, siRNA knockdown, minigene assays Molecular and cellular biology High 19047369
2010 SRp20 (SRSF3) and 9G8 interact with TAP/NXF1 and mediate export of viral HSV-1 RNA; siRNA knockdown of SRp20 causes ~10-fold decrease in virus yields and nuclear accumulation of poly(A)+ RNA in infected cells. siRNA knockdown, poly(A)+ RNA localization, virus yield assays Virology Medium 20227104
2010 EBV SM protein directly interacts with SRp20 (SRSF3); affinity purification and mass spectrometry identified the interaction, and the SRp20 interaction is required for SM-mediated alternative splicing of STAT1 pre-mRNA, as SRp20 overexpression enhances and knockdown inhibits SM splicing activity. Affinity purification, mass spectrometry, co-immunoprecipitation, siRNA, STAT1 splicing assay Journal of virology High 20810723
2011 SRp20 (SRSF3) dramatically re-localizes from the nucleus to the cytoplasm during poliovirus infection, co-localizes with PCBP2 on the viral IRES RNA, and functions in viral IRES-mediated translation initiation; a mutant SRp20 lacking the RRM causes ~100-fold decrease in virus yield as a dominant negative. Immunofluorescence, co-immunoprecipitation, RNA immunoprecipitation, dominant negative mutagenesis PLoS pathogens High 21779168
2012 Poliovirus 2A proteinase expression is sufficient to cause nucleocytoplasmic redistribution of SRp20 (SRSF3) through cleavage of nuclear pore proteins; similar redistribution occurs during coxsackievirus B3 infection. Proteinase expression, immunofluorescence, nuclear pore protein cleavage assay Journal of virology Medium 23255796
2015 PTBP1 and PTBP2 bind to an exonic splicing suppressor in SRSF3 exon 4 and inhibit its inclusion, thereby impairing SRSF3 autoregulation and causing SRSF3 overexpression in cancer cells; SRSF3 in turn promotes PTBP2 expression, forming a regulatory circuit. RNA binding assays, overexpression, knockdown, RT-PCR splicing assays Scientific reports Medium 26416554
2019 Palmitic acid-induced oxidative stress causes NEDD8 conjugation (neddylation) of SRSF3 at lysine 11, leading to proteasome-mediated degradation; mutation of K11 (SRSF3-K11R) is sufficient to prevent both degradation and downstream splicing alterations in hepatocytes. Site-directed mutagenesis, ubiquitination/neddylation assays, proteasome inhibition, in vivo mouse model The Journal of clinical investigation High 31393851
2014 KSHV ORF57 protein binds to the RRM of SRSF3 via its N-terminal half, preventing SRSF3 from associating with a suboptimal K8β intron RNA; this attenuates the suppressive effect of SRSF3 on K8β splicing and promotes RNA splicing. SPEN proteins suppress ORF57 activity by displacing ORF57 from SRSF3-RNA complexes. Co-immunoprecipitation, RNA immunoprecipitation, domain mapping, splicing assays RNA (New York, N.Y.) High 25234929
2018 SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by directly binding to an RNA sequence on exon 8; RNA pulldown confirmed direct binding to wild-type but not mutant exon 8 sequence, and mutagenesis of the SRSF3 binding site on exon 8 disrupts SRSF3-mediated exon 9 skipping. siRNA knockdown, overexpression, mutagenesis, RNA pulldown/immunoblot Biochimica et biophysica acta High 24321384
2017 SRSF3 associates with the 3' UTR of highly upregulated innate immune mRNAs in activated microglia and suppresses their translation through a 3' UTR-mediated mechanism, creating a dissociation between mRNA and protein levels during innate immune challenge. Ribosome profiling (translational state analysis), in vivo microglial activation model Cell reports Medium 29241548
2019 Cardiomyocyte-specific loss of SRSF3 causes alternative splicing of mTOR mRNA to generate a shorter catalytically inactive isoform, leading to decreased 4E-BP1 phosphorylation, increased mRNA decapping of sarcomeric and calcium-handling protein mRNAs, and severe systolic dysfunction causing death within 8 days. Inducible cardiomyocyte-specific KO mouse, RNA-Seq, mTOR activity assays, decapping assays Circulation research High 31145021
2021 SRSF3 modulates 3' UTR length by promoting distal polyadenylation site usage directly (by counteracting SRSF7) and indirectly by maintaining high levels of cleavage factor Im (CFIm) through alternative splicing; SRSF3 binds upstream of proximal poly(A) sites as determined by iCLIP. iCLIP, 3'-end sequencing, SRSF3/SRSF7 knockdown, domain swap experiments Genome biology High 33706811
2018 SRSF3 maintains transcriptome integrity in mouse oocytes by regulating alternative splicing and repressing B2 SINE transposable elements; conditional deletion of Srsf3 in germinal vesicle oocytes compromises germinal vesicle breakdown (GVBD) and meiotic entry due to both aberrant alternative splicing and transposable element derepression. Conditional oocyte-specific KO, 3D time-lapse live imaging, single-cell RNA-seq, antisense oligonucleotides Cell discovery High 29928511
2018 TDP43 and SRSF3 form a complex that co-regulates specific alternative splicing events in triple-negative breast cancer, including splicing of PAR3 and NUMB exon 12; the TDP43/SRSF3 complex was identified by deep sequencing and co-immunoprecipitation. RNA-seq, co-immunoprecipitation, siRNA knockdown, functional assays Proceedings of the National Academy of Sciences of the United States of America Medium 29581274
2018 SRSF3 is functionally connected to the nuclear RNA exosome for degradation of intronless mRNAs: SRSF3 interacts with the RNA exosome and its adaptor complex NEXT, participating in destabilization of viral mRNAs from intronless genes in the absence of the viral stabilizing protein EB2. Co-immunoprecipitation, RNA immunoprecipitation, mRNA stability assays Scientific reports Medium 30150655
2021 Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRα signaling in mouse palatal mesenchyme cells, leading to nuclear translocation of Srsf3; ablation of Srsf3 in neural crest causes facial clefting due to defective proliferation and survival, and Srsf3 regulates alternative splicing of transcripts encoding protein kinases. Phosphorylation assays, conditional KO mouse, RNA-seq splicing analysis, live cell imaging Development (Cambridge, England) High 34184034
2021 PPM1G phosphatase interacts with SRSF3 and promotes its dephosphorylation, altering alternative splicing patterns of cell-cycle and transcription-related genes in hepatocellular carcinoma cells. Co-immunoprecipitation, phosphorylation assays, overexpression/knockdown, RNA splicing analysis Cell death & disease Medium 34290239
2019 SRSF3 regulates alternative splicing of ILF3 pre-mRNA by binding to RNA sequence motifs to control exclusion/inclusion of ILF3 exon 18 or selection of an alternative 3' splice site, producing distinct ILF3 isoforms with opposing effects on cell proliferation and apoptosis. RNA binding assays, minigene splicing assays, overexpression/knockdown RNA (New York, N.Y.) Medium 30796096
2019 Truncated forms of SRSF3 (SRSF3-TR) generated by aberrant splicing act as dominant negatives or gain-of-function proteins that impair correct splicing of SRSF1/ASF-SF2 and the sister chromatid cohesion protein sororin, causing R-loop formation, DNA damage, and mitotic derangements; SLU7 keeps SRSF3-TR in check. siRNA knockdown, splicing assays, R-loop detection, cell cycle analysis Nucleic acids research Medium 30657957
2022 hnRNPH1 recruits PTBP2 and SRSF3 to form a complex that modulates alternative splicing in germ cells; conditional knockout of Hnrnph1 in spermatogenic cells causes aberrant splicing of meiosis-related genes and leads to male sterility. Co-immunoprecipitation, conditional KO mouse, RNA-seq splicing analysis Nature communications High 35739118
2022 Loss of SRSF3 in megakaryocytes leads to nuclear accumulation of megakaryocyte mRNAs and failure to load platelets with RNAs required for normal platelet function, demonstrating SRSF3-mediated mRNA export is essential for megakaryocyte maturation and platelet production; megakaryocyte-specific Srsf3 KO causes macrothrombocytopenia. Megakaryocyte-specific conditional KO mouse, RNA-seq, mRNA localization assays Blood High 34852174
2023 SRSF3 and SRSF7 stimulate Microprocessor cleavage of pri-miRNAs through CRC and CNNC motifs adopting specific secondary structures, and both factors affect Microprocessor cleavage sites in human cells; SRSF7 can also stimulate Microprocessor independently. High-throughput pri-miRNA cleavage assays, mutagenesis, secondary structure analysis Life science alliance High 36750366
2023 Loss of SRSF3 in hepatocytes impairs lipophagy by promoting proteasomal degradation of syntaxin 17 (STX17), a key autophagosomal SNARE protein required for autophagosome-lysosome fusion; ubiquitination of STX17 is increased via upregulation of SIAH1. Hepatocyte SRSF3 KO, ubiquitination assays, autophagy flux assays, STX17 stability assays Journal of lipid research Medium 36764525
2015 SRSF3 regulates a HER2 splicing hotspot in breast cancer; RNA chromatography assays demonstrated direct binding of SRSF3 to RNA in the HER2 exon 15 region at two specific binding sites, and SRSF3 knockdown switches splice variants from the oncogenic Δ16HER2 to the growth-inhibitory p100 isoform. RNA chromatography, siRNA knockdown, RT-PCR splice variant analysis RNA biology Medium 26367347
2008 Beta-catenin/TCF4 signaling directly transcriptionally activates the SRp20 (SRSF3) gene promoter; increased SRp20 protein levels resulting from this signaling are sufficient to modulate alternative splicing of endogenous targets including CD44. Luciferase reporter assay, dominant-negative TCF4, beta-catenin overexpression, splicing assay RNA (New York, N.Y.) Medium 18952824
2005 Insulin stimulation induces proteasome-dependent degradation of SRp20 (SRSF3) in human hematopoietic cells, as demonstrated by 2D electrophoresis proteomics confirmed by 1D Western blotting and MG-132 proteasome inhibitor rescue. 2D-electrophoresis proteomics, Western blot, proteasome inhibitor treatment American journal of physiology. Endocrinology and metabolism Medium 15827065
2006 Nuclear PLCβ1 physically interacts with SRp20 (SRSF3) in the nucleus, as demonstrated by immunoprecipitation; overexpression of nuclear PLCβ1 downregulates SRp20 expression. Co-immunoprecipitation, subcellular fractionation, 2D-electrophoresis proteomics Proteomics Low 17022104
2012 Srp20 (SRSF3) overexpression increases inclusion of exon 19 in TrkB minigene transcripts (generating TrkB-Shc) and increases endogenous TrkB-Shc:TrkB-TK+ mRNA ratio; conversely, Srp20 knockdown produces opposite effects, placing Srp20 as a direct regulator of TrkB pre-mRNA splicing relevant to Alzheimer's disease. Minigene transfection, overexpression, siRNA knockdown, RT-PCR Journal of neurochemistry Medium 22788679
2018 SRSF3 controls PKM pre-mRNA splicing in colon cancer cells by cooperating with PTBP1 and hnRNPA1; silencing SRSF3 increases the PKM1/PKM2 ratio, causing a metabolic shift from glycolysis to oxidative phosphorylation; protein complex formation among SRSF3, PTBP1, and hnRNPA1 was validated by RIP and immunoprecipitation. RNP immunoprecipitation (RIP), immunoprecipitation, metabolic analysis, siRNA knockdown International journal of molecular sciences Medium 30279379
2025 SRSF3 forms part of a nuclear pore export complex with ALYREF and XPO5 (exportin-5), recruited by phase-separating YTHDC1 to assist nuclear export of m6A-modified lncRNA. Co-immunoprecipitation, phase separation assays, RNA export assays Cell death & disease Low 40221424

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Molecular cell 318 11336712
1997 The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation. The EMBO journal 226 9305649
1999 The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers. RNA (New York, N.Y.) 192 10094314
2010 SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance. International journal of biological sciences 174 21179588
2018 CircSMARCA5 Inhibits Migration of Glioblastoma Multiforme Cells by Regulating a Molecular Axis Involving Splicing Factors SRSF1/SRSF3/PTB. International journal of molecular sciences 163 29415469
2006 RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. Nature structural & molecular biology 159 17028590
1998 Regulation of alternative polyadenylation by U1 snRNPs and SRp20. Molecular and cellular biology 158 9710581
2009 Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation. Molecular cell 148 19250906
1999 Blastocyst formation is blocked in mouse embryos lacking the splicing factor SRp20. Current biology : CB 138 10469594
2012 Downregulation of splicing factor SRSF3 induces p53β, an alternatively spliced isoform of p53 that promotes cellular senescence. Oncogene 135 22777358
2013 Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function. Nature communications 127 23299886
2006 Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8. The EMBO journal 127 17036044
2021 FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells. BMC biology 95 34433435
2019 Degradation of splicing factor SRSF3 contributes to progressive liver disease. The Journal of clinical investigation 95 31393851
2022 SRSF3-mediated regulation of N6-methyladenosine modification-related lncRNA ANRIL splicing promotes resistance of pancreatic cancer to gemcitabine. Cell reports 91 35545048
2010 Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer. Oncogene 91 20856201
2004 Alternative splicing of the multidrug resistance protein 1/ATP binding cassette transporter subfamily gene in ovarian cancer creates functional splice variants and is associated with increased expression of the splicing factors PTB and SRp20. Clinical cancer research : an official journal of the American Association for Cancer Research 91 15269137
2008 SRp20 and CUG-BP1 modulate insulin receptor exon 11 alternative splicing. Molecular and cellular biology 87 19047369
2018 Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3. Proceedings of the National Academy of Sciences of the United States of America 84 29581274
2018 SRSF3, a Splicer of the PKM Gene, Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells. International journal of molecular sciences 84 30279379
2019 SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Cancer research 83 31462429
2008 Control of the papillomavirus early-to-late switch by differentially expressed SRp20. Journal of virology 79 18945760
2020 Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3. Brain : a journal of neurology 78 33141183
1997 Regulated expression and RNA processing of transcripts from the Srp20 splicing factor gene during the cell cycle. Molecular and cellular biology 76 9154810
2017 Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts. Cell reports 74 29241548
2015 SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells. RNA biology 72 26367347
2013 Splicing factor SRSF3 represses the translation of programmed cell death 4 mRNA by associating with the 5'-UTR region. Cell death and differentiation 70 24292556
2018 SRSF3 recruits DROSHA to the basal junction of primary microRNAs. RNA (New York, N.Y.) 68 29615481
2015 PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells. Scientific reports 65 26416554
2003 The CD44 alternative v9 exon contains a splicing enhancer responsive to the SR proteins 9G8, ASF/SF2, and SRp20. The Journal of biological chemistry 63 12826680
2022 hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells. Nature communications 60 35739118
2010 SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. Virology 58 20227104
2013 SRp20: an overview of its role in human diseases. Biochemical and biophysical research communications 57 23685143
2008 The beta-catenin/TCF4 pathway modifies alternative splicing through modulation of SRp20 expression. RNA (New York, N.Y.) 57 18952824
2019 Splicing events in the control of genome integrity: role of SLU7 and truncated SRSF3 proteins. Nucleic acids research 56 30657957
2018 SRSF5 functions as a novel oncogenic splicing factor and is upregulated by oncogene SRSF3 in oral squamous cell carcinoma. Biochimica et biophysica acta. Molecular cell research 56 29857020
2011 Re-localization of cellular protein SRp20 during poliovirus infection: bridging a viral IRES to the host cell translation apparatus. PLoS pathogens 56 21779168
2019 Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction. Circulation research 55 31145021
2012 The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B. RNA (New York, N.Y.) 55 22456266
2019 Oncogenic splicing factor SRSF3 regulates ILF3 alternative splicing to promote cancer cell proliferation and transformation. RNA (New York, N.Y.) 52 30796096
2010 Global analysis reveals SRp20- and SRp75-specific mRNPs in cycling and neural cells. Nature structural & molecular biology 52 20639886
2010 Epstein-Barr Virus SM protein utilizes cellular splicing factor SRp20 to mediate alternative splicing. Journal of virology 52 20810723
2021 SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels. Genome biology 50 33706811
2017 RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell. Biochimica et biophysica acta. Molecular cell research 50 29138007
2012 Protein cross-talk in CD133+ colon cancer cells indicates activation of the Wnt pathway and upregulation of SRp20 that is potentially involved in tumorigenicity. Proteomics 49 22623141
2020 Emerging Roles of SRSF3 as a Therapeutic Target for Cancer. Frontiers in oncology 48 33072610
2018 SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements. Cell discovery 47 29928511
2021 PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3. Cell death & disease 46 34290239
2015 Serine/arginine-rich splicing factor 3 (SRSF3) regulates homologous recombination-mediated DNA repair. Molecular cancer 45 26282282
2014 Attenuation of the suppressive activity of cellular splicing factor SRSF3 by Kaposi sarcoma-associated herpesvirus ORF57 protein is required for RNA splicing. RNA (New York, N.Y.) 43 25234929
2017 Theophylline exhibits anti-cancer activity via suppressing SRSF3 in cervical and breast cancer cell lines. Oncotarget 42 29254178
2019 Alternative polyadenylation dependent function of splicing factor SRSF3 contributes to cellular senescence. Aging 41 30835716
2016 Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma. International journal of medical sciences 40 27429590
2012 Viral proteinase requirements for the nucleocytoplasmic relocalization of cellular splicing factor SRp20 during picornavirus infections. Journal of virology 40 23255796
2020 SRSF3: Newly discovered functions and roles in human health and diseases. European journal of cell biology 39 32800280
2005 Proteomic analysis on insulin signaling in human hematopoietic cells: identification of CLIC1 and SRp20 as novel downstream effectors of insulin. American journal of physiology. Endocrinology and metabolism 36 15827065
2007 Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation. Learning & memory (Cold Spring Harbor, N.Y.) 33 17911373
2000 Regulation of SRp20 exon 4 splicing. Biochimica et biophysica acta 33 11072076
2019 Cortisol-induced SRSF3 expression promotes GR splicing, RACK1 expression and breast cancer cells migration. Pharmacological research 32 30862604
2016 HnRNP L is important for the expression of oncogene SRSF3 and oncogenic potential of oral squamous cell carcinoma cells. Scientific reports 32 27808105
2012 Srp20 regulates TrkB pre-mRNA splicing to generate TrkB-Shc transcripts with implications for Alzheimer's disease. Journal of neurochemistry 32 22788679
2006 Proteomic-based analysis of nuclear signaling: PLCbeta1 affects the expression of the splicing factor SRp20 in Friend erythroleukemia cells. Proteomics 32 17022104
2017 MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3. Oncotarget 31 28039456
2012 Epstein-Barr virus protein EB2 stimulates cytoplasmic mRNA accumulation by counteracting the deleterious effects of SRp20 on viral mRNAs. Nucleic acids research 31 22505578
2020 Aberrant expression and regulatory network of splicing factor-SRSF3 in tumors. Journal of Cancer 28 32284746
2013 Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8. Biochimica et biophysica acta 28 24321384
2019 Downregulation of SRSF3 by antisense oligonucleotides sensitizes oral squamous cell carcinoma and breast cancer cells to paclitaxel treatment. Cancer chemotherapy and pharmacology 27 31515668
2018 The splicing factor SRSF3 is functionally connected to the nuclear RNA exosome for intronless mRNA decay. Scientific reports 27 30150655
2016 SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation. Biochemical and biophysical research communications 27 26773498
2018 Amiodarone promotes cancer cell death through elevated truncated SRSF3 and downregulation of miR-224. Oncotarget 26 29568365
2013 BRG1 variant rs1122608 on chromosome 19p13.2 confers protection against stroke and regulates expression of pre-mRNA-splicing factor SFRS3. Human genetics 26 24190014
2008 Increased expression of splicing factor SRp20 mRNA in bipolar disorder patients. Journal of affective disorders 25 18281098
2022 A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis. Cell death discovery 24 35501301
2015 Regulation of CD44E by DARPP-32-dependent activation of SRp20 splicing factor in gastric tumorigenesis. Oncogene 24 26119931
2021 Biological function and molecular mechanism of SRSF3 in cancer and beyond. Oncology letters 21 34858525
2019 Oncogene SRSF3 suppresses autophagy via inhibiting BECN1 expression. Biochemical and biophysical research communications 21 30654935
2020 B7-H3 is spliced by SRSF3 in colorectal cancer. Cancer immunology, immunotherapy : CII 20 32719950
2017 SRSF3-regulated miR-132/212 controls cell migration and invasion by targeting YAP1. Experimental cell research 20 28624413
2013 Cardiac glycosides correct aberrant splicing of IKBKAP-encoded mRNA in familial dysautonomia derived cells by suppressing expression of SRSF3. The FEBS journal 20 23711097
2001 Splicing factor SRP20 is a novel partner of BCL6 in a t(3;6)(q27;p21) translocation in transformed follicular lymphoma. Genes, chromosomes & cancer 20 11579468
2022 CircRNA SRRM4 affects glucose metabolism by regulating PKM alternative splicing via SRSF3 deubiquitination in epilepsy. Neuropathology and applied neurobiology 19 36168302
2018 RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis. International journal of molecular sciences 19 30200638
2023 Oncogenic SRSF3 in health and diseases. International journal of biological sciences 18 37416784
2021 Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme. Development (Cambridge, England) 18 34184034
2018 Trichostatin a Protects Dendritic Cells Against Oxygen-Glucose Deprivation via the SRSF3/PKM2/Glycolytic Pathway. Frontiers in pharmacology 18 29942258
2013 Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein. Virus research 18 23830997
2024 Circular RNA hsa_circ_0050386 suppresses non-small cell lung cancer progression via regulating the SRSF3/FN1 axis. Journal of translational medicine 16 38216996
2022 The RNA-binding protein SRSF3 has an essential role in megakaryocyte maturation and platelet production. Blood 16 34852174
2020 SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30. Cancer cell international 16 32308565
2018 Inhibition of the expression of oncogene SRSF3 by blocking an exonic splicing suppressor with antisense oligonucleotides. RSC advances 16 35540349
2005 Isolation of SFRS3 gene and its differential expression during metamorphosis involving eye migration of Japanese flounder Paralichthys olivaceus. Biochimica et biophysica acta 16 15950387
2023 LincRNA-EPS Alleviates Inflammation in TMJ Osteoarthritis by Binding to SRSF3. Journal of dental research 15 37464762
2022 SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma. International journal of molecular sciences 15 36499164
2025 YTHDC1 phase separation drives the nuclear export of m6A-modified lncNONMMUT062668.2 through the transport complex SRSF3-ALYREF-XPO5 to aggravate pulmonary fibrosis. Cell death & disease 13 40221424
2020 The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism. Neoplasia (New York, N.Y.) 12 33142236
2022 SRSF3 facilitates replication of influenza A virus via binding and promoting the transport of viral mRNA. Veterinary microbiology 11 35063826
2023 SRSF7 and SRSF3 depend on RNA sequencing motifs and secondary structures to regulate Microprocessor. Life science alliance 10 36750366
2023 Loss of Splicing Factor SRSF3 Impairs Lipophagy Through Ubiquitination and Degradation of Syntaxin17 in Hepatocytes. Journal of lipid research 10 36764525
2022 Splicing factor SRSF3 promotes the progression of cervical cancer through regulating DDX5. Molecular carcinogenesis 10 36282044
2013 Regulation of cellular RNA nano-particle assembly by splicing factor SRp20. Journal of nanoscience and nanotechnology 10 23646715