Affinage

SRSF3

Serine/arginine-rich splicing factor 3 · UniProt P84103

Length
164 aa
Mass
19.3 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 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

SRSF3 (SRp20) is a multifunctional SR-family RNA-binding protein that governs pre-mRNA splicing and couples it to downstream steps of RNA metabolism, recognizing CA-rich/CAUC RNA elements through its RRM in which the 5' cytosine is the principal specificity determinant (PMID:17036044, PMID:10094314). As a sequence-specific splicing transactivator it controls constitutive and alternative exon choice across many transcripts, including its own pre-mRNA—where it enhances inclusion of the exon 4 that encodes a truncated, RS-domain-less product, an autoregulatory loop antagonized by ASF/SF2 (PMID:9305649, PMID:10094314). Its splicing decisions are read out on physiologically critical substrates: it directs TP53 isoform choice to restrain senescence (PMID:22777358), insulin receptor exon 11 inclusion antagonistically with CUG-BP1 (PMID:19047369), and caspase-2 exon skipping (PMID:24321384), and it acts within multiprotein splicing complexes with partners such as TDP43, PTBP1/hnRNPA1, and hnRNP H1 (PMID:29581274, PMID:30279379, PMID:26367347). Beyond splicing, SRSF3 links transcript processing to nuclear export—an arginine-rich peptide adjacent to the RRM contacts the export receptor TAP/NXF1 to drive export of intronless and polyadenylated mRNAs (PMID:17036044, PMID:11336712)—and to 3'-end processing, where it promotes distal poly(A) site usage and long 3'UTRs by counteracting SRSF7 and sustaining CFIm levels (PMID:33706811, PMID:30835716). It additionally stimulates Microprocessor cleavage of pri-miRNAs by recruiting DROSHA in a CNNC-motif- and position-dependent manner (PMID:29615481, PMID:36750366), and represses translation of specific mRNAs such as PDCD4 via 5'UTR binding and P-body sequestration (PMID:24292556, PMID:23646715). SRSF3 activity is constrained by post-translational control, including Aurora B-driven H3 Ser10 phosphorylation that releases it from mitotic chromosomes (PMID:19250906) and NEDD8 conjugation at Lys11 that triggers its proteasomal degradation under lipotoxic stress (PMID:31393851). Genetically, SRSF3 is non-redundant for mouse development and tissue maturation: its loss blocks blastocyst formation (PMID:10469594), impairs hepatocyte maturation and glucose/lipid homeostasis (PMID:23299886), disrupts oocyte meiotic entry with transposon derepression (PMID:29928511), blocks megakaryocyte maturation and platelet RNA loading (PMID:34852174), and in cardiomyocytes triggers an mTOR mis-splicing/4E-BP1/decapping cascade causing fatal heart failure (PMID:31145021).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Established that SRSF3 is not merely a generic splicing factor but autoregulates its own abundance, defining a feedback principle for SR-protein homeostasis.

    Evidence Reporter/minigene constructs with overexpression in transfected cells

    PMID:9305649

    Open questions at the time
    • Did not define the RNA element bound
    • Physiological consequence of the truncated isoform unaddressed
  2. 1999 High

    Defined the RNA sequence specificity and confirmed SRSF3 acts as a sequence-directed splicing transactivator, linking binding to function.

    Evidence SELEX, UV cross-linking, IP and S100 in vitro complementation with recombinant protein

    PMID:10094314

    Open questions at the time
    • No atomic-resolution basis for specificity yet
    • Endogenous target repertoire unknown
  3. 1999 High

    Demonstrated SRSF3 is non-redundant in vivo, showing an essential developmental requirement distinct from other SR proteins.

    Evidence Cre-loxP conditional knockout mice with immunofluorescence

    PMID:10469594

    Open questions at the time
    • Molecular targets driving the morula arrest not identified
  4. 1998 High

    Extended SRSF3 function beyond splice-site choice to 3'-terminal exon/polyadenylation control, an early hint of its role in 3'-end processing.

    Evidence Wild-type and RS-domain-deletion mutants with polyadenylation factor (CstF) binding assays

    PMID:9710581

    Open questions at the time
    • Direct SRSF3-CstF contact not structurally defined
  5. 2001 High

    Identified SRSF3 as an export factor for intronless mRNAs, coupling RNA recognition to nucleocytoplasmic transport.

    Evidence UV cross-linking, Xenopus oocyte microinjection and antibody inhibition across two cell systems

    PMID:11336712

    Open questions at the time
    • Export receptor contact not yet mapped at this stage
  6. 2006 High

    Resolved the structural basis of RNA recognition and the molecular adaptor for export, showing a dedicated arginine-rich peptide contacts TAP/NXF1 independent of RNA binding.

    Evidence NMR solution structure of RRM-CAUC complex plus peptide mutagenesis and TAP binding assays

    PMID:17036044

    Open questions at the time
    • Full-length protein/RS-domain contributions to export not structurally resolved
  7. 2006 High

    Connected SRSF3 recruitment to transcription machinery, showing the RNA pol II CTD directs SRSF3-mediated exon skipping independent of elongation rate.

    Evidence Alpha-amanitin-resistant CTD mutants with fibronectin reporter minigenes

    PMID:17028590

    Open questions at the time
    • Direct CTD-SRSF3 contact and adaptor not identified
  8. 2009 High

    Revealed cell-cycle regulation of SRSF3 chromatin association, linking Aurora B/H3S10 phosphorylation to its mitotic release.

    Evidence Aurora B inhibition, chromatin fractionation, siRNA knockdown and immunofluorescence

    PMID:19250906

    Open questions at the time
    • Functional consequence of mitotic eviction for daughter-cell splicing unknown
  9. 2010 Medium

    Mapped genome-wide endogenous mRNA targets and showed they shift with differentiation, establishing SRSF3 as a context-dependent post-transcriptional regulator.

    Evidence GFP-tagged SR protein immunopurification with genome-wide target ID and knockdown/rescue in P19 cells

    PMID:20639886

    Open questions at the time
    • Single lab
    • Direct vs indirect targets not distinguished
  10. 2012 High

    Identified TP53 isoform splicing as a direct SRSF3 target controlling senescence, providing a tumor-relevant functional output.

    Evidence CLIP, RNA pulldown, TP53 minigene and epistasis with p53 knockdown

    PMID:22777358

    Open questions at the time
    • Only partial rescue by p53 depletion implies additional effectors
  11. 2013 High

    Showed SRSF3 controls hepatocyte maturation and metabolic gene splicing in vivo, defining a tissue-specific physiological role.

    Evidence Hepatocyte-specific conditional knockout mice with splicing analysis of Hnf1a, Ern1, Hmgcs1, Dhcr7, Scap

    PMID:23299886

    Open questions at the time
    • Which mis-spliced target is causal for the architecture defect unresolved
  12. 2013 Medium

    Established a direct translational-repression function of SRSF3 distinct from splicing, via 5'UTR binding and P-body sequestration of PDCD4.

    Evidence Polysome profiling, live-cell imaging, RNA reporters and knockdown/overexpression

    PMID:23646715 PMID:24292556

    Open questions at the time
    • Generality across mRNAs and the P-body recruitment mechanism not defined
  13. 2018 High

    Defined a non-splicing role in miRNA biogenesis, with SRSF3 recruiting DROSHA to pri-miRNA basal junctions in a motif- and position-dependent manner.

    Evidence Engineered pri-miRNA substrates and Microprocessor cleavage/recruitment assays

    PMID:29615481 PMID:36750366

    Open questions at the time
    • Endogenous miRNA repertoire dependence on SRSF3 in vivo incompletely mapped
  14. 2018 Medium

    Placed SRSF3 in multiprotein splicing complexes (TDP43, PTBP1/hnRNPA1, hnRNP H1) controlling cancer- and germline-relevant exons.

    Evidence Reciprocal Co-IP, RNA-seq, RIP and knockdown with functional splicing readouts

    PMID:29581274 PMID:30279379 PMID:35739118

    Open questions at the time
    • Stoichiometry and assembly order of these complexes undefined
    • SRSF3 not directly manipulated in some studies
  15. 2019 High

    Identified neddylation at Lys11 as a stress-triggered degradation switch coupling lipotoxicity to SRSF3-dependent splicing changes.

    Evidence Neddylation assays, K11R mutagenesis, proteasome inhibition and in vivo mouse steatosis model

    PMID:31393851

    Open questions at the time
    • Identity of the responsible NEDD8 E3 ligase not defined
  16. 2019 High

    Defined a cardiomyocyte SRSF3→mTOR splicing→4E-BP1→decapping axis whose disruption causes lethal heart failure, linking SRSF3 splicing to mRNA stability and translation control.

    Evidence Inducible cardiomyocyte-specific knockout, RNA-seq, Western blot and mTOR-activation rescue

    PMID:31145021

    Open questions at the time
    • Direct SRSF3 binding on mTOR pre-mRNA not mapped
  17. 2021 High

    Resolved SRSF3's role in alternative polyadenylation, showing it promotes long 3'UTRs both directly against SRSF7 and indirectly via CFIm maintenance.

    Evidence iCLIP and 3'-end sequencing with knockdown and SRSF3/SRSF7 domain comparison

    PMID:30835716 PMID:33706811

    Open questions at the time
    • Determinants of proximal vs distal PAS choice on individual genes incomplete
  18. 2021 High

    Connected upstream signaling to SRSF3 localization, with Akt phosphorylation downstream of PDGFRα/PI3K driving nuclear translocation and craniofacial development.

    Evidence Phosphorylation assays, neural-crest conditional knockout mice and splicing analysis

    PMID:34184034 PMID:34290239

    Open questions at the time
    • Phosphatase (PPM1G) versus kinase balance in vivo not fully integrated
  19. 2022 High

    Demonstrated SRSF3 is required for megakaryocyte maturation and proper RNA sorting into platelets, extending its export/localization role to hematopoiesis.

    Evidence Megakaryocyte-specific knockout mice with RNA-seq and mRNA localization analysis

    PMID:34852174

    Open questions at the time
    • Mechanism of cytoplasmic RNA sorting into platelets undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SRSF3's many regulatory outputs (splicing, export, APA, miRNA biogenesis, translation) are coordinately selected within a given cell, and which targets are causal for each tissue phenotype, remains unresolved.
  • No unified model linking post-translational state to functional output
  • Causal target hierarchy per tissue not established
  • Recruitment logic switching SRSF3 between activities unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0140110 transcription regulator activity 5 GO:0045182 translation regulator activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-392499 Metabolism of proteins 3
Partners
DROSHAHNRNPH1NXF1PCBP2PPM1GPTBP1SRSF7TDP43
Complex memberships
Microprocessor (with DROSHA)TDP43/SRSF3 splicing complexhnRNPH1/PTBP2/SRSF3 complexnuclear RNA exosome/NEXT

Evidence

Reading pass · 49 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. 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 regulates alternative splicing of its own pre-mRNA by enhancing recognition of the weak splice acceptor of exon 4, leading to exon 4 inclusion and production of a truncated protein lacking the RS domain. ASF/SF2 antagonizes this autoregulation by suppressing use of the exon 4 splice donor. Reporter gene constructs, overexpression, transfection assays The EMBO journal High 9305649
1999 The RNA recognition motif (RRM) of SRp20 recognizes sequences similar to those selected by mutated zinc-knuckle 9G8, and SRp20 acts as an efficient splicing transactivator through its specific RNA targets. Recombinant SRp20 activates splicing in vitro of heterologous exons containing its binding sequences. SELEX, UV cross-linking, immunoprecipitation, S100 complementation with recombinant proteins RNA (New York, N.Y.) High 10094314
1998 SRp20 affects alternative 3'-terminal exon recognition in the calcitonin/CGRP gene via enhancing CstF binding to the alternative polyadenylation site. Wild-type SRp20 enhances exon 4 inclusion, while a mutant lacking the RS domain inhibits exon 4 inclusion by inhibiting CstF binding to the poly(A) site. Transfection with wild-type and mutant SRp20, polyadenylation factor binding assays Molecular and cellular biology High 9710581
2006 The C-terminal domain (CTD) of RNA polymerase II is required for the inhibitory action of SRp20 on inclusion of a fibronectin cassette exon. The CTD promotes exon skipping by recruiting SRp20 in a manner that is independent of effects on transcription elongation rate. Alpha-amanitin-resistant pol II CTD mutants, fibronectin reporter minigenes Nature structural & molecular biology High 17028590
2006 SRp20 and 9G8 contain a short arginine-rich peptide adjacent to their RRMs that does not contact RNA but is necessary and sufficient for interaction with the mRNA export factor TAP/NXF1. NMR solution structure of SRp20 RRM in complex with 5'CAUC3' RNA revealed that all 4 nt are contacted but only the 5' cytosine is specifically recognized. NMR solution structure, binding assays, peptide mutagenesis The EMBO journal High 17036044
1999 SRp20 is essential for mouse development; knockout mice fail to form blastocysts and die at the morula stage. Immunofluorescent staining showed SRp20 is present in oocytes and early embryonic stages, demonstrating a non-redundant function among SR proteins. Cre-loxP conditional knockout in mice, immunofluorescence staining Current biology : CB High 10469594
2009 SRp20 and ASF/SF2 associate with interphase chromatin but are released from hyperphosphorylated mitotic chromosomes. Aurora B kinase-mediated histone H3 serine 10 phosphorylation is the mechanism driving this dissociation, as Aurora B inhibition increased SRp20 and ASF/SF2 retention on mitotic chromosomes. siRNA knockdown, Aurora B kinase inhibition, chromatin fractionation, immunofluorescence Molecular cell High 19250906
2012 SRSF3 regulates alternative splicing of TP53 pre-mRNA by binding (via CLIP and RNA pulldown) to the alternatively spliced exon uniquely included in p53β mRNA. Knockdown of SRSF3 induces inclusion of the p53β-specific exon, upregulates p53β protein, and promotes cellular senescence; p53 knockdown partially rescues SRSF3-knockdown-induced senescence. siRNA knockdown, RNA pulldown assays, CLIP, TP53 minigene splicing assay Oncogene High 22777358
2013 Hepatocyte-specific deletion of Srsf3 in mice disrupts hepatic architecture and causes impaired hepatocyte maturation with alterations in glucose and lipid homeostasis. Loss of SRSF3 causes aberrant splicing of Hnf1α, Ern1, Hmgcs1, Dhcr7, and Scap, which are critical regulators of glucose and lipid metabolism. Hepatocyte-specific conditional knockout mice, splicing analysis Nature communications High 23299886
2019 Palmitic acid-induced oxidative stress causes NEDD8 conjugation (neddylation) to SRSF3 at lysine 11, leading to proteasome-mediated degradation. The K11R mutation prevents both SRSF3 degradation and alterations in RNA splicing, and prevention of SRSF3 degradation in vivo partially protects mice from hepatic steatosis, fibrosis and inflammation. Neddylation assay, site-directed mutagenesis (K11R), proteasome inhibitor treatment, in vivo mouse model The Journal of clinical investigation High 31393851
2018 SRSF3 recruits DROSHA to the basal junction of primary microRNA transcripts (pri-miRNAs) in a CNNC-motif-dependent manner, enhancing Microprocessor cleavage activity. This stimulation only occurs when CNNC is located ~17 nt from the Microprocessor cleavage site. Pri-miRNA substrate engineering, Microprocessor cleavage assays, SRSF3-DROSHA recruitment assays RNA (New York, N.Y.) High 29615481
2013 SRSF3 represses translation of PDCD4 mRNA by directly binding to its 5'-UTR. SRSF3 co-localizes with PDCD4 mRNA in P-bodies in live cells; SRSF3 silencing shifts PDCD4 mRNA to translating polysome fractions, and overexpression shifts it to non-translating fractions. Also regulates alternative splicing pattern of PDCD4 pre-mRNA. Polysome profiling, live cell imaging, RNA reporter systems, siRNA knockdown/overexpression Cell death and differentiation High 24292556
2011 SRp20 dramatically re-localizes from the nucleus to the cytoplasm during poliovirus infection and partially co-localizes with PCBP2. SRp20 is found in viral translation initiation complexes bound to poliovirus RNA via PCBP2. A mutant SRp20 lacking the RNA recognition motif (SRp20ΔRRM) causes ~100-fold decrease in virus yield, demonstrating the RRM is required for IRES-dependent translation. Immunofluorescence co-localization, co-immunoprecipitation, dominant-negative mutant expression, virus yield assays PLoS pathogens High 21779168
2008 SRp20 and CUG-BP1 act antagonistically to regulate insulin receptor exon 11 alternative splicing. SRp20 binds to exonic splicing enhancers in exon 11 (identified by RNA affinity chromatography) and promotes exon inclusion; overexpression/knockdown confirmed this. The relative ratio of SRp20 to CUG-BP1 in different cells determines degree of exon inclusion. Minigene linker-scanning mutagenesis, RNA affinity chromatography, overexpression and knockdown Molecular and cellular biology High 19047369
2015 PTBP1 and PTBP2 bind to an exonic splicing suppressor in SRSF3 exon 4 and inhibit its inclusion, resulting in overexpression of full-length functional SRSF3. Overexpressed SRSF3 in turn promotes PTBP2 expression, forming a regulatory circuit that impairs SRSF3 autoregulation in cancer cells. RNA binding assays, overexpression/knockdown, RT-PCR splicing analysis Scientific reports Medium 26416554
2010 SRp20 promotes nucleocytoplasmic export of HSV-1 mRNAs. siRNA knockdown of SRp20 resulted in ~10-fold decrease in HSV-1 virus yields and nuclear accumulation of polyA+ RNA and newly transcribed viral RNA. SRp20 interacts with export receptor TAP/NXF1. siRNA knockdown, virus yield assays, nuclear/cytoplasmic RNA fractionation, BrU-labeled RNA tracking Virology Medium 20227104
2010 EBV SM protein interacts with SRp20 (identified by affinity purification and mass spectrometry) and recruits/co-opts SRp20 function in alternative splicing of STAT1 pre-mRNA. SRp20 overexpression enhanced SM-mediated alternative splicing; SRp20 knockdown inhibited the SM splicing effect. The interaction regions of SM and SRp20 were mapped by in vitro and in vivo assays. Affinity purification, mass spectrometry, co-immunoprecipitation, overexpression and knockdown, STAT1 splicing assay Journal of virology Medium 20810723
2014 KSHV ORF57 N-terminal half binds to the RNA recognition motif of SRSF3, preventing SRSF3 from associating with the K8β intron RNA. In the absence of ORF57, SRSF3 binds to a suboptimal K8β intron and inhibits splicing; knockdown of SRSF3 promotes K8β splicing mimicking ORF57. ORF57 also promotes splicing of heterologous transcripts negatively regulated by SRSF3. Co-immunoprecipitation, RNA binding assays, siRNA knockdown, splicing reporter assays RNA (New York, N.Y.) High 25234929
2019 Loss of SRSF3 in cardiomyocytes causes alternative splicing of mTOR mRNA generating a shorter isoform lacking catalytic activity, decreased 4E-BP1 phosphorylation, and consequently increased decapping of mRNAs encoding sarcomeric and calcium-handling proteins, leading to severe systolic dysfunction and death within 8 days. mTOR activation partially reverses decapping. Inducible cardiomyocyte-specific Srsf3 knockout mice, RNA-Seq, Western blotting, mTOR activation rescue Circulation research High 31145021
2018 SRSF3 is an essential regulator of alternative splicing and transposable element repression in mouse oocytes. Conditional deletion of Srsf3 compromises germinal vesicle breakdown (GVBD) and meiotic entry. The GVBD defect is caused by both aberrant alternative splicing and derepression of B2 SINE transposable elements. Conditional oocyte-specific knockout, 3D time-lapse confocal live imaging, single-cell RNA-seq, antisense oligonucleotides, RNase-H gapmers Cell discovery High 29928511
2008 SRp20 controls the papillomavirus early-to-late switch by interacting with A/C-rich RNA elements (SE4) and suppressing selection of a late-specific BPV-1 splice site. SRp20 levels inversely correlate with L1 capsid protein expression; abundant SRp20 in undifferentiated keratinocytes promotes viral early E6/E7 expression by enhancing SP1 transcription factor expression. RNA-protein binding assays, transfection of BPV-1/HPV constructs, raft culture differentiation, knockdown/overexpression Journal of virology Medium 18945760
2008 Beta-catenin/TCF4 signaling activates SRp20 gene transcription; activated beta-catenin mutants increase endogenous SRp20 transcript and protein and stimulate an SRp20 promoter luciferase reporter. The beta-catenin/TCF4-mediated increase in SRp20 protein is sufficient to modulate alternative splicing of CD44 and a control minigene. Transfection of activated beta-catenin mutants, dominant-negative TCF4, luciferase reporter, endogenous splicing analysis RNA (New York, N.Y.) Medium 18952824
2010 SRp20 and SRp75 associate with hundreds of distinct, functionally related endogenous mRNA targets in cycling and neurally induced P19 cells, with mRNA target profiles changing in response to neural differentiation. Knockdown of SRp20 led to up- or downregulation of specific target transcripts. GFP-tagged SR protein immunopurification, genome-wide mRNA target identification, knockdown with GFP rescue Nature structural & molecular biology Medium 20639886
2012 Poliovirus 2A proteinase expression is sufficient to cause nucleocytoplasmic redistribution of SRp20 by cleaving specific nuclear pore proteins. Coxsackievirus B3 similarly relocalizes SRp20 to the cytoplasm. Human rhinovirus 16 2A proteinase alone can efficiently cause SRp20 cytoplasmic relocalization despite lower relocalization during actual rhinovirus infection. 2A proteinase expression constructs, nuclear pore protein cleavage analysis, immunofluorescence Journal of virology Medium 23255796
2019 Truncated forms of SRSF3 (SRSF3-TR), generated when splicing regulator SLU7 is knocked down, impair correct splicing and expression of SRSF1/ASF/SF2 and the sister chromatid cohesion protein sororin, acting as dominant negatives or via gain-of-function. This pathway links SLU7 to genome stability maintenance. siRNA knockdown (SLU7), RT-PCR splicing analysis, mouse liver in vivo validation Nucleic acids research Medium 30657957
2017 In activated microglia, SRSF3 suppresses translation of highly upregulated innate immune transcripts through a 3' UTR-mediated mechanism. Ribosome profiling in vivo revealed dissociation between the mRNA and protein networks, with SRSF3 acting as a translational checkpoint for pro-inflammatory mRNAs. In vivo ribosome profiling (translational state analysis), innate immune challenge model Cell reports Medium 29241548
2018 TDP43 and SRSF3 form a complex (TDP43/SRSF3) that controls specific alternative splicing events including PAR3 (controlling metastasis) and NUMB exon 12 (controlling proliferation) in triple-negative breast cancer. Deep sequencing revealed most TDP43-regulated splicing events involve SRSF3. Co-immunoprecipitation, RNA-seq, knockdown experiments with specific splicing readouts Proceedings of the National Academy of Sciences of the United States of America Medium 29581274
2018 SRSF3 regulates PKM pre-mRNA alternative splicing (exon skipping to favor PKM2 over PKM1) in colon cancer cells in cooperation with PTBP1 and hnRNPA1. This was validated by RNP immunoprecipitation and co-immunoprecipitation. SRSF3 silencing increases the PKM1/PKM2 ratio and causes a metabolic shift from glycolysis to oxidative phosphorylation. RNP immunoprecipitation (RIP), co-immunoprecipitation, siRNA knockdown, metabolic analysis International journal of molecular sciences Medium 30279379
2015 SRSF3 and hnRNP H1 regulate alternative splicing at a HER2 splicing hotspot. SRSF3 knockdown switches splicing from the oncogenic Δ16HER2 variant to the anti-proliferative p100 variant. SRSF3 directly binds RNA within HER2 exon 15, with two binding sites identified by RNA chromatography. siRNA knockdown, RNA chromatography binding assays RNA biology Medium 26367347
2021 SRSF3 and SRSF7 bind upstream of proximal polyadenylation sites and have opposing effects on 3'UTR length: SRSF3 promotes distal PAS usage (long 3'UTRs) directly by counteracting SRSF7, and indirectly by maintaining high levels of cleavage factor Im (CFIm) via alternative splicing. Upon SRSF3 depletion, CFIm levels decrease and 3'UTRs are shortened. iCLIP, 3'-end sequencing, siRNA knockdown, domain analysis comparing SRSF3 and SRSF7 Genome biology High 33706811
2019 SRSF3 regulates alternative RNA splicing of ILF3 by binding to RNA sequence motifs, controlling exclusion/inclusion of ILF3 exon 18 or selection of an alternative 3' splice site within exon 18. Reduced SRSF3 leads to production of aberrant ILF3 isoforms 5 and 7 that suppress cell proliferation. RNA binding assays, minigene splicing assays, overexpression and knockdown RNA (New York, N.Y.) Medium 30796096
2021 Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRα signaling in mouse palatal mesenchyme cells, leading to its nuclear translocation. Ablation of Srsf3 in neural crest lineage leads to facial clefting due to defective cranial neural crest cell proliferation and survival. Srsf3 regulates alternative RNA splicing of transcripts encoding protein kinases to modulate PDGFRα-dependent intracellular signaling. Phosphorylation assays, conditional neural crest knockout mice, alternative splicing analysis Development (Cambridge, England) High 34184034
2021 PPM1G protein phosphatase interacts with SRSF3, promotes its dephosphorylation, and changes alternative splicing patterns of cell cycle and transcriptional regulation genes in hepatocellular carcinoma cells. Co-immunoprecipitation, overexpression/knockdown, phosphorylation assays, alternative splicing analysis Cell death & disease Medium 34290239
2022 SRSF3 is essential for megakaryocyte maturation and platelet production. Megakaryocyte-specific deletion of Srsf3 leads to macrothrombocytopenia and megakaryocyte maturation arrest. SRSF3 depletion leads to nuclear accumulation of megakaryocyte mRNAs, and SRSF3 plays a role in sorting cytoplasmic megakaryocyte RNAs into platelets. Megakaryocyte-specific conditional knockout mice, RNA-seq, mRNA localization analysis Blood High 34852174
2018 SRSF3 connects alternative polyadenylation with mRNA export. SRSF3 depletion caused preference for proximal poly(A) sites and global 3'UTR shortening associated with senescence-associated pathways. SRSF3 has higher binding density near proximal poly(A) sites than distal ones in 3'UTR-shortened genes. siRNA knockdown, 3'UTR length analysis, SRSF3 binding density analysis, overexpression of candidate genes Aging Medium 30835716
2018 SRSF3 is functionally connected to the nuclear RNA exosome for degradation of intronless mRNAs. SRSF3 interacts with both the RNA exosome and its adaptor complex NEXT to promote degradation of intronless viral and cellular mRNAs in the nucleus. Co-immunoprecipitation of SRSF3 with exosome and NEXT complex, RNA stability assays Scientific reports Medium 30150655
2013 SRp20 promotes exon 9 skipping of caspase-2 pre-mRNA by directly binding to a specific sequence on exon 8 (but not mutant sequences), as demonstrated by RNA pulldown. Deletion of 26 nt from exon 8 potential binding site severely disrupts SRSF3-mediated exon 9 skipping. siRNA knockdown, overexpression, RNA pulldown, deletion and substitution mutagenesis Biochimica et biophysica acta Medium 24321384
2013 Srp20 (SRp20) overexpression increases inclusion of TrkB exon 19 (generating TrkB-Shc transcript) in a TrkB minigene system, and Srp20 knockdown produces the opposite effect. Amyloid beta 1-42 increases Srp20 mRNA levels in SHSY5Y cells, suggesting Srp20 mediates Aβ-induced TrkB splicing changes relevant to Alzheimer's disease. TrkB minigene transfection, Srp20 overexpression and knockdown, Aβ treatment Journal of neurochemistry Medium 22788679
2012 EBV EB2 protein counteracts SRp20 by enhancing SRp20 association with beta-globin transcripts (shown by RNA-immunoprecipitation), apparently stabilizing labile SRp20-RNA interactions to prevent SRp20-mediated mRNA destabilization. SRp20 depletion increases cytoplasmic accumulation of intronless mRNAs, suggesting SRp20 normally destabilizes these RNAs. siRNA knockdown, RNA immunoprecipitation (RIP), mRNA accumulation assay Nucleic acids research Medium 22505578
2023 SRSF7 and SRSF3 stimulate Microprocessor cleavage of pri-miRNAs through CRC and CNNC motifs adopting specific secondary structures. Both factors affect Microprocessor cleavage sites in human cells. High-throughput pri-miRNA cleavage assays defined the structural requirements for SRSF3-mediated Microprocessor enhancement. High-throughput pri-miRNA cleavage assays, Microprocessor assays with SRSF3/SRSF7, human cell experiments Life science alliance High 36750366
2019 SRSF3 inhibits expression of BECN1 (Beclin-1), a key autophagy regulator, by suppressing expression of p65 and FoxO1 upstream of BECN1. Overexpression of SRSF3 inhibits hypoxia-induced autophagy while knockdown increases autophagic activity. Knockdown and overexpression, hypoxia-induced autophagy assay, gene expression analysis Biochemical and biophysical research communications Low 30654935
2005 Insulin stimulation causes proteasome-dependent reduction in SRp20 levels in human hematopoietic cells, identifying SRp20 as a downstream effector of insulin signaling degraded via the proteasome. 2D electrophoresis proteomic analysis, Western blotting, MG-132 proteasome inhibitor treatment American journal of physiology. Endocrinology and metabolism Medium 15827065
2006 Nuclear PLCbeta1 physically interacts with SRp20 in the nucleus (demonstrated by co-immunoprecipitation and subcellular fractionation), and overexpression of nuclear PLCbeta1 downregulates SRp20 expression. Co-immunoprecipitation, subcellular fractionation, 2D Western blotting Proteomics Low 17022104
2022 SRSF3 promotes influenza A virus replication by binding to viral mRNA and participating in its nuclear-cytoplasmic transport. The 88th amino acid of SRSF3 is required for this function. SRSF3 knockdown reduces viral replication. RIP, FISH, overexpression/knockdown, site-directed mutagenesis (aa88), virus replication assays Veterinary microbiology Medium 35063826
2020 SRSF3 silencing in glioblastoma cells decreased aggressiveness in vitro and in vivo, likely through a molecular mechanism involving PDGFRB and PI3K-AKT/ERK signaling pathways, possibly involving altered alternative splicing of TP73 transcription factor controlling PDGFRB. siRNA knockdown, in vitro aggressiveness assays, in vivo tumor growth, splicing analysis Brain : a journal of neurology Medium 33141183
2023 Loss of SRSF3 in hepatocytes impairs lipophagy (selective autophagy of lipid droplets) 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 upon SRSF3 loss. siRNA knockdown, lipophagy assays, ubiquitination assays, protein stability analysis Journal of lipid research Medium 36764525
2013 SRp20 is a structural component of stress granules (SGs) and P-bodies (PBs). Knockdown of SRp20 disrupts RNA granule formation. SRp20 is distributed across all ribosomal fractions in polysome profiling, suggesting a role in post-transcriptional cytoplasmic mRNA regulation through RNA granules. Immunofluorescence microscopy, siRNA knockdown, polysome profiling Journal of nanoscience and nanotechnology Medium 23646715
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 events affecting meiosis-related genes and germ-Sertoli cell communication, leading to infertility. SRSF3 is part of the hnRNPH1 splicing regulatory complex. Co-immunoprecipitation, conditional knockout mice, splicing analysis, fertility phenotype Nature communications Medium 35739118

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 319 11336712
1997 The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation. The EMBO journal 229 9305649
1999 The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers. RNA (New York, N.Y.) 193 10094314
2010 SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance. International journal of biological sciences 175 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 164 29415469
1998 Regulation of alternative polyadenylation by U1 snRNPs and SRp20. Molecular and cellular biology 160 9710581
2006 RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. Nature structural & molecular biology 159 17028590
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 140 10469594
2012 Downregulation of splicing factor SRSF3 induces p53β, an alternatively spliced isoform of p53 that promotes cellular senescence. Oncogene 137 22777358
2013 Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function. Nature communications 129 23299886
2006 Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8. The EMBO journal 128 17036044
2021 FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells. BMC biology 100 34433435
2019 Degradation of splicing factor SRSF3 contributes to progressive liver disease. The Journal of clinical investigation 97 31393851
2022 SRSF3-mediated regulation of N6-methyladenosine modification-related lncRNA ANRIL splicing promotes resistance of pancreatic cancer to gemcitabine. Cell reports 95 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 86 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
2020 Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3. Brain : a journal of neurology 80 33141183
2008 Control of the papillomavirus early-to-late switch by differentially expressed SRp20. Journal of virology 80 18945760
1997 Regulated expression and RNA processing of transcripts from the Srp20 splicing factor gene during the cell cycle. Molecular and cellular biology 77 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 73 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 72 24292556
2018 SRSF3 recruits DROSHA to the basal junction of primary microRNAs. RNA (New York, N.Y.) 69 29615481
2015 PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells. Scientific reports 67 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 62 35739118
2010 SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. Virology 59 20227104
2013 SRp20: an overview of its role in human diseases. Biochemical and biophysical research communications 58 23685143
2008 The beta-catenin/TCF4 pathway modifies alternative splicing through modulation of SRp20 expression. RNA (New York, N.Y.) 58 18952824
2019 Splicing events in the control of genome integrity: role of SLU7 and truncated SRSF3 proteins. Nucleic acids research 57 30657957
2019 Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction. Circulation research 57 31145021
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 57 29857020
2011 Re-localization of cellular protein SRp20 during poliovirus infection: bridging a viral IRES to the host cell translation apparatus. PLoS pathogens 57 21779168
2012 The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B. RNA (New York, N.Y.) 56 22456266
2010 Epstein-Barr Virus SM protein utilizes cellular splicing factor SRp20 to mediate alternative splicing. Journal of virology 55 20810723
2021 SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels. Genome biology 53 33706811
2010 Global analysis reveals SRp20- and SRp75-specific mRNPs in cycling and neural cells. Nature structural & molecular biology 53 20639886
2019 Oncogenic splicing factor SRSF3 regulates ILF3 alternative splicing to promote cancer cell proliferation and transformation. RNA (New York, N.Y.) 52 30796096
2018 SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements. Cell discovery 52 29928511
2017 RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell. Biochimica et biophysica acta. Molecular cell research 51 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 50 22623141
2020 Emerging Roles of SRSF3 as a Therapeutic Target for Cancer. Frontiers in oncology 49 33072610
2021 PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3. Cell death & disease 47 34290239
2015 Serine/arginine-rich splicing factor 3 (SRSF3) regulates homologous recombination-mediated DNA repair. Molecular cancer 45 26282282
2017 Theophylline exhibits anti-cancer activity via suppressing SRSF3 in cervical and breast cancer cell lines. Oncotarget 44 29254178
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.) 44 25234929
2019 Alternative polyadenylation dependent function of splicing factor SRSF3 contributes to cellular senescence. Aging 42 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
2012 Epstein-Barr virus protein EB2 stimulates cytoplasmic mRNA accumulation by counteracting the deleterious effects of SRp20 on viral mRNAs. Nucleic acids research 33 22505578
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
2018 The splicing factor SRSF3 is functionally connected to the nuclear RNA exosome for intronless mRNA decay. Scientific reports 30 30150655
2020 Aberrant expression and regulatory network of splicing factor-SRSF3 in tumors. Journal of Cancer 28 32284746
2019 Downregulation of SRSF3 by antisense oligonucleotides sensitizes oral squamous cell carcinoma and breast cancer cells to paclitaxel treatment. Cancer chemotherapy and pharmacology 28 31515668
2016 SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation. Biochemical and biophysical research communications 28 26773498
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
2022 A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis. Cell death discovery 26 35501301
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
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 22 34858525
2020 B7-H3 is spliced by SRSF3 in colorectal cancer. Cancer immunology, immunotherapy : CII 21 32719950
2019 Oncogene SRSF3 suppresses autophagy via inhibiting BECN1 expression. Biochemical and biophysical research communications 21 30654935
2017 SRSF3-regulated miR-132/212 controls cell migration and invasion by targeting YAP1. Experimental cell research 21 28624413
2023 Oncogenic SRSF3 in health and diseases. International journal of biological sciences 20 37416784
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
2021 Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme. Development (Cambridge, England) 19 34184034
2018 RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis. International journal of molecular sciences 19 30200638
2022 The RNA-binding protein SRSF3 has an essential role in megakaryocyte maturation and platelet production. Blood 18 34852174
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 17 38216996
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
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 15 40221424
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
2022 SRSF3 facilitates replication of influenza A virus via binding and promoting the transport of viral mRNA. Veterinary microbiology 12 35063826
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
2023 SRSF7 and SRSF3 depend on RNA sequencing motifs and secondary structures to regulate Microprocessor. Life science alliance 11 36750366
2023 Loss of Splicing Factor SRSF3 Impairs Lipophagy Through Ubiquitination and Degradation of Syntaxin17 in Hepatocytes. Journal of lipid research 11 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

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