Affinage

SRSF2

Serine/arginine-rich splicing factor 2 · UniProt Q01130

Length
221 aa
Mass
25.5 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 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

SRSF2 (SC35) is an essential SR-family pre-mRNA splicing factor that recognizes degenerate exonic splicing enhancers through its RRM and promotes spliceosome assembly, splice-site selection, and exon inclusion across many tissue-specific programs (PMID:1373910, PMID:1454802). It was originally isolated as a factor required for the first step of splicing and for spliceosome assembly, reconstituting splicing activity in S100 and immunodepleted extracts where it favors proximal splice sites in antagonism with hnRNP A1 (PMID:1373910, PMID:1454802), and it can substitute for U2AF65 to recruit U2 snRNP in a substrate-specific, U1 snRNP-dependent manner (PMID:8990173). Sequence-specificity studies and solution NMR structures of the RRM define a high-affinity 5'-SSNG-3' consensus, with the protein binding 5'-UCCAGU-3' and 5'-UGGAGU-3' equally by flipping central C or G bases between anti and syn conformations and with the elongated L3 loop essential for RNA contact (PMID:10629063, PMID:22002536, PMID:22140111); the RRM also serves as a reader of m5C-modified mRNA, with NSUN2-deposited m5C enhancing SRSF2 binding (PMID:38065062). Beyond splicing, SRSF2 facilitates transcriptional elongation by promoting P-TEFb recruitment and CTD Ser2 phosphorylation (PMID:18641664) and autoregulates its own expression through alternative splicing of its terminal exon coupled to mRNA surveillance (PMID:11285241, PMID:19965769). Its activity is tuned by post-translational control, including Tip60-mediated K52 acetylation that drives proteasomal degradation and HDAC6/SRPK opposition (PMID:21157427). Genetically, SRSF2 is required for T cell maturation, cardiac and hepatic homeostasis, and myogenesis, regulating defined targets such as CD45, RyR2, and stress-death pathway genes (PMID:11239462, PMID:14963485, PMID:27022105, PMID:35460187). Recurrent Pro95 hot-spot mutations (e.g., P95H) cause myelodysplastic/myeloproliferative neoplasms by shifting RNA-binding specificity toward UCCAG over UGGAG motifs, mis-splicing hematopoietic regulators including EZH2 and HNRNPA2B1, enhancing EJC-dependent nonsense-mediated decay, impairing m5C reading, and disrupting mitochondrial mRNA splicing such that PINK1-mediated mitophagy becomes essential for mutant-cell survival (PMID:25965569, PMID:26261309, PMID:29858584, PMID:32001512, PMID:38065062, PMID:38713535).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Established SRSF2's foundational identity by showing it is a splicing factor required for the first catalytic step and spliceosome assembly, defining it as an SR-family protein.

    Evidence cDNA cloning and in vitro splicing reconstitution revealing an RNP RNA-binding motif and a C-terminal SR domain; recombinant protein reconstitutes splicing and favors proximal splice sites antagonized by hnRNP A1

    PMID:1373910 PMID:1454802

    Open questions at the time
    • RNA sequence specificity not yet defined
    • Mechanism of splice-site proximity bias not resolved structurally
  2. 1997 High

    Showed SRSF2 can recruit U2 snRNP independently of U2AF65, revealing an alternative pathway for early spliceosome assembly.

    Evidence U2AF affinity depletion from HeLa extracts and reconstitution with recombinant SC35

    PMID:8990173

    Open questions at the time
    • Substrate determinants of U2AF-independence unknown
    • Generality across pre-mRNAs untested
  3. 2000 High

    Defined SRSF2's distinct functional RNA specificity, separating it from SF2/ASF and establishing it recognizes a dedicated ESE class.

    Evidence In vitro functional SELEX under splicing conditions with S100/nuclear-extract complementation

    PMID:10629063 PMID:7543047

    Open questions at the time
    • Structural basis of specificity not yet known
    • Relationship to in vivo binding sites unresolved
  4. 2001 High

    Revealed SRSF2 autoregulates its abundance, defining a feedback circuit coupling its own splicing to mRNA surveillance.

    Evidence Overexpression, in vitro splicing, siRNA knockdown and mRNA stability assays in HeLa; effect specific to SC35

    PMID:11285241

    Open questions at the time
    • Trans-factors antagonizing autoregulation not fully mapped at this stage
  5. 2001 High

    Demonstrated SRSF2 is a physiological splicing regulator in vivo, controlling tissue-specific programs and cell maturation.

    Evidence Conditional KO in thymus with CD45 isoform RT-PCR; later conditional KOs in heart (RyR2), MEFs (p53/SirT1 pathway), liver, and muscle

    PMID:11239462 PMID:14963485 PMID:17526736 PMID:35460187

    Open questions at the time
    • Whether phenotypes reflect splicing vs transcriptional elongation roles not always separated
    • Full target spectrum per tissue incomplete
  6. 2008 High

    Linked SRSF2 to transcriptional elongation, establishing a role beyond splicing in coupling RNA Pol II activity to processing.

    Evidence siRNA depletion with Pol II/P-TEFb ChIP and recombinant-SC35-rescued nuclear run-on showing CTD Ser2 phosphorylation control

    PMID:18641664

    Open questions at the time
    • Direct interaction with P-TEFb not biochemically defined
    • Mechanism of CTD kinase recruitment unresolved
  7. 2010 High

    Defined post-translational control of SRSF2 abundance and activity, showing acetylation/phosphorylation balance governs splicing-dependent cell fate.

    Evidence In vitro acetylation, K52 mutagenesis, Co-IP and knockdown showing Tip60 acetylation drives degradation while HDAC6 stabilizes; SRPK nuclear translocation regulation; caspase-8 splicing readout

    PMID:21157427

    Open questions at the time
    • Stoichiometry of acetylation in vivo unknown
    • Interplay with phosphorylation site occupancy not quantified
  8. 2011 High

    Provided the structural basis for SRSF2 RNA recognition, explaining its degenerate SSNG specificity through base-flipping and an atypical L3 loop.

    Evidence Solution NMR structures of free and RNA-bound RRM with mutagenesis, ITC, and functional splicing validation

    PMID:22002536 PMID:22140111

    Open questions at the time
    • Structure of full-length protein with RS domain not determined
    • Basis for in vivo site selection beyond consensus unresolved
  9. 2015 High

    Established that Pro95 hot-spot mutations are change-of-function alleles that reprogram RNA-binding specificity to drive myeloid neoplasia.

    Evidence Conditional knockin mice, CRISPR isogenic K562 cells, RNA gel shifts and RNA-seq showing UCCAG-favoring/UGGAG-disfavoring shift, EZH2 mis-splicing/NMD, and hematopoietic differentiation defects

    PMID:25965569 PMID:26124281 PMID:26261309

    Open questions at the time
    • Full set of disease-driving targets not defined
    • Why HSC context is required for transformation unexplained at this stage
  10. 2018 High

    Refined the mutant mechanism by showing much mis-splicing is indirect, propagating through mis-regulation of other RNA-processing factors.

    Evidence HITS-CLIP and RNA-seq in mutant cells with in vivo differentiation assay implicating HNRNPA2B1 mis-splicing; physiological knockin MDS/MPN model

    PMID:29858584 PMID:29903888

    Open questions at the time
    • Hierarchy of direct vs cascade targets incompletely ordered
    • Contribution of each downstream factor not quantified
  11. 2020 High

    Connected mutant SRSF2 to enhanced nonsense-mediated decay through EJC deposition, defining a degradation arm of its oncogenic program.

    Evidence RNA-seq, EJC deposition assays, and antisense-oligonucleotide rescue in isogenic mutant cells

    PMID:32001512

    Open questions at the time
    • Generality of EJC-coupled decay across mutant targets unresolved
    • Therapeutic window of ASO rescue untested clinically
  12. 2023 High

    Identified SRSF2 as an m5C reader, adding an RNA-modification-dependent layer to its binding and explaining a further defect of the P95H mutant.

    Evidence m5C-RIP, structural identification of recognition residues with mutagenesis, NSUN2 knockdown with RNA-seq and CLIP-seq

    PMID:38065062

    Open questions at the time
    • Genome-wide overlap of m5C reading with classical ESE binding unresolved
    • Contribution of m5C reading to disease phenotype not quantified
  13. 2024 High

    Revealed a mitochondrial vulnerability of mutant cells, showing PINK1-mediated mitophagy becomes essential when SRSF2 P95H disrupts mitochondrial mRNA splicing.

    Evidence RNA-seq of mitochondrial mRNA splicing, complex I activity assays, PINK1 splicing reporter, GSK-3 inhibitor and apoptosis assays in isogenic mutant cells

    PMID:38713535

    Open questions at the time
    • Whether mitophagy dependency is therapeutically exploitable untested in vivo
    • Mechanism coupling mitochondrial dysfunction to PINK1 intron removal incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SRSF2's splicing, transcriptional elongation, m5C-reading, and autoregulatory activities are integrated and differentially deployed across normal tissues versus mutant disease states remains unresolved.
  • No unified model reconciling direct vs cascade targets in disease
  • Structure of full-length protein in complex with spliceosome unknown
  • Tissue-specific determinants of target selection undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140098 catalytic activity, acting on RNA 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
DYRK1AEP300KAT5NONOSFPQSRPK1TBX5

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 SC35 (SRSF2) was isolated as a splicing factor required for the first step of the splicing reaction and for spliceosome assembly; its cDNA revealed it contains an RNP-type RNA binding motif and a C-terminal SR domain, making it a member of the SR protein family. cDNA cloning, in vitro splicing reconstitution assay Science High 1373910
1992 Recombinant SC35 can reconstitute splicing activity in S100 extracts and in SC35-immunodepleted nuclear extracts; SC35 favors proximal 5' and 3' splice sites, an effect antagonized by hnRNP A1. In vitro splicing reconstitution assay with recombinant proteins and immunodepleted extracts Proceedings of the National Academy of Sciences High 1454802
1995 SC35 and ASF/SF2 have distinct, functionally significant RNA binding specificities determined by SELEX; the arginine-serine region is not the major determinant of specificity. Unlike ASF/SF2, a SC35 high-affinity binding site element did not function as a splicing enhancer in S100 complementation assays. SELEX, RNA binding assays, in vitro splicing complementation The EMBO journal High 7543047
1997 SC35 can functionally substitute for U2AF65 in reconstituting pre-mRNA splicing in U2AF-depleted HeLa nuclear extracts, in a substrate-specific and U1 snRNP-dependent manner, demonstrating a U2AF-independent pathway for U2 snRNP recruitment. Affinity depletion of U2AF from nuclear extracts, in vitro splicing reconstitution with recombinant SC35 Proceedings of the National Academy of Sciences High 8990173
2000 A novel ESE motif recognized by SC35 under splicing conditions was identified by in vitro functional SELEX; SC35-selected sequences promote splicing in nuclear extract or S100 complemented by SC35 but not by SF2/ASF, demonstrating distinct and functional RNA sequence specificity. In vitro SELEX under splicing conditions, in vitro splicing assays in S100 and nuclear extracts Molecular and cellular biology High 10629063
2001 SC35 autoregulates its own expression by activating specific alternative splicing events in the 3' UTR of its own pre-mRNA, producing unstable mRNA isoforms subject to mRNA surveillance; this effect is specific to SC35 and not shared by ASF/SF2 or 9G8. Overexpression in HeLa cells, in vitro splicing with recombinant SR proteins, siRNA knockdown, mRNA stability assays The EMBO journal High 11285241
2001 Cre-mediated conditional deletion of SC35 in the thymus causes a defect in T cell maturation and alters alternative splicing of CD45 (a receptor tyrosine phosphatase), establishing SC35 as a physiological regulator of a T cell-specific splicing pathway. Conditional knockout mouse (Cre-lox), RT-PCR for CD45 isoforms Molecular cell High 11239462
2003 GSK-3 phosphorylates SC35 in vitro (on a peptide from its SR domain requiring priming phosphorylation) and affects its intranuclear distribution; GSK-3 inhibition in neurons redistributes SC35 to nuclear speckles and increases tau exon 10 inclusion. In vitro kinase assay with recombinant GSK-3β, immunoprecipitation of SC35, immunofluorescence, RT-PCR for tau splicing The Journal of biological chemistry Medium 14602710
2004 Tissue-specific ablation of SC35 in the heart causes dilated cardiomyopathy preceded by downregulation of cardiac ryanodine receptor 2 (RyR2), with mutant cardiomyocytes showing frequency-dependent excitation-contraction coupling defects. Conditional knockout mouse (MLC-2v-Cre), microarray, RT-PCR, calcium imaging The EMBO journal High 14963485
2005 SC35 is responsible for aberrant splicing of E1alpha pyruvate dehydrogenase mRNA caused by a disease mutation: the mutation increases SC35 binding to a cryptic splice donor, and siRNA-mediated reduction of SC35 in patient fibroblasts abolishes the aberrant splice product. RNA binding assays, overexpression, siRNA knockdown in patient fibroblasts, RT-PCR Molecular and cellular biology High 15798212
2007 Loss of SC35 in mouse embryonic fibroblasts induces G2/M cell cycle arrest and genomic instability via p53 hyperphosphorylation (linked to ATM activation) and hyperacetylation (attributed to increased p300 expression and aberrant SirT1 splicing); SC35 also controls cell proliferation during pituitary gland development but is dispensable in mature cardiomyocytes. Conditional knockout mouse, cell cycle analysis, immunoblotting for p53 modifications, RT-PCR for SirT1 splicing Molecular and cellular biology High 17526736
2008 SC35 depletion induces RNA Pol II accumulation within gene bodies and attenuated transcriptional elongation, correlated with defective P-TEFb recruitment and dramatically reduced CTD Ser2 phosphorylation; recombinant SC35 rescues this elongation defect in nuclear run-on experiments. siRNA depletion, ChIP for Pol II and P-TEFb, nuclear run-on assay with recombinant SC35 Nature structural & molecular biology High 18641664
2008 E2F1 transcriptionally upregulates SC35 (SRSF2) expression; SC35 is required for E2F1-induced switching of alternative splicing of apoptotic genes (c-FLIP, caspase-8, caspase-9, Bcl-x) toward pro-apoptotic splice variants and for apoptosis in response to DNA-damaging agents. ChIP for E2F1 at SRSF2 promoter, siRNA knockdown of SC35, RT-PCR for splice isoforms, apoptosis assays Cell death and differentiation High 18806759
2009 SC35 promotes tau exon 10 inclusion by binding to a SC35-like exonic splicing enhancer on tau pre-mRNA; mutation of this element abolishes both SC35 binding and exon inclusion. Dyrk1A phosphorylates SC35 in vitro and interacts with SC35 in cells, and overexpression of Dyrk1A suppresses SC35's ability to promote tau exon 10 inclusion. Co-immunoprecipitation, in vitro kinase assay, minigene splicing assay, mutation analysis Nucleic acids research High 21470964
2009 The SC35 terminal intron self-regulation involves exonic splicing enhancer elements in the last exon that respond specifically to SC35; hnRNP H and TDP-43 antagonize SC35 binding to the terminal exon and repress SC35 terminal 3' splice site usage. Minigene splicing assays, RNA binding competition assays, in vitro and in cellulo splicing Nucleic acids research Medium 19965769
2010 Tip60 acetyltransferase acetylates SRSF2 on lysine 52 (within the RRM), promoting its proteasomal degradation; HDAC6 deacetylase counters this acetylation and acts as a positive regulator of SRSF2 protein level. Tip60 also downregulates SRSF2 phosphorylation by inhibiting nuclear translocation of SRPK1 and SRPK2. This acetylation/phosphorylation network controls caspase-8 pre-mRNA splicing and cell fate in response to cisplatin. In vitro acetylation assay, site-directed mutagenesis (K52), co-immunoprecipitation, siRNA knockdown, RT-PCR for caspase-8 isoforms The EMBO journal High 21157427
2011 The solution NMR structure of SRSF2 RRM bound to 5'-UCCAGU-3' and 5'-UGGAGU-3' RNA reveals a sandwich-like structure; SRSF2 binds both sequences equally by flipping the two central C or G bases into anti or syn conformation. The L3 loop is crucial for RNA binding (NMR/mutagenesis). The high-affinity consensus is 5'-SSNG-3' (S=C/G), validated by in vitro and in vivo splicing assays. NMR structure determination, mutagenesis, ITC/binding assays, in vitro and in vivo splicing assays The EMBO journal High 22002536
2011 The solution structure of the free SRSF2 RRM (residues 9-101) was determined; unlike other SR proteins, SRSF2 has a longer L3 loop and lacks the conserved aromatic residue in RNP2. The L3 loop (in addition to canonical β1/β3 strands) is essential for RNA binding, shown by NMR chemical shift perturbation and mutagenesis; RNA 5'-AGCAGAGUA-3' binds with Kd = 61 nM. NMR structure determination, ITC, site-directed mutagenesis Nucleic acids research High 22140111
2011 SC35 binds tau exon 10 mRNA via the SC35-like element and stabilizes tau mRNA (specifically exon 10-containing isoforms) without affecting tau transcription, thereby promoting tau protein expression. RNA immunoprecipitation (RIP), mRNA stability assay, RT-PCR, overexpression FEBS letters Medium 21333649
2013 SRSF2 promotes splicing and transcription of exon 11-included isoform of the Ron proto-oncogene by binding to a CGAG sequence on exon 11; mutation of this sequence abolishes both physical interaction and splicing promotion. Knockdown/overexpression, RT-PCR, RNA pull-down/mutation analysis Biochimica et biophysica acta Medium 25220236
2015 SRSF2 mutations (e.g., P95H) alter SRSF2's sequence-specific RNA binding activity, changing recognition of specific ESE motifs to drive recurrent mis-splicing of hematopoietic regulators including EZH2 (triggering NMD), thereby impairing hematopoietic differentiation in vivo. Conditional knockin mouse, RNA-seq, in vivo differentiation assays, splicing reporter assays Cancer cell High 25965569
2015 SRSF2 P95H mutation introduced by CRISPR into K562 cells alters RNA binding affinity in a motif-specific manner: mutant SRSF2 binds UCCAG sites more tightly and UGGAG sites less tightly than wild-type, causing corresponding increased or decreased exon inclusion; protein-protein interactions with key splicing factors are unaffected by the mutation. CRISPR knockin, RNA gel shift assays, RNA-seq for splicing changes, co-immunoprecipitation Proceedings of the National Academy of Sciences High 26261309
2015 Ablation of SRSF2 in the hematopoietic lineage causes embryonic lethality with enhanced apoptosis and decreased hematopoietic stem/progenitor cells; adult conditional knockout shows decreased LSK cells; MDS-associated P95H and P95-R102 deletion mutations cause significant changes in alternative splicing of genes enriched in cancer and apoptosis. Conditional knockout mouse (Mx1-Cre), RNA-seq for splicing changes, HSPC flow cytometry Molecular and cellular biology High 26124281
2017 SRSF2 binding within an alternative exon is associated with its inclusion, whereas SRSF2 binding in a flanking constitutive exon is associated with exclusion of the alternative exon; SRSF2 regulates alternative splicing driving hepatocellular carcinoma progression. CLIP-seq/RNA-seq, knockdown/overexpression, RT-PCR for splice isoforms Cancer research Medium 28082404
2017 Liver-specific deletion of SRSF2 (but not SRSF1) causes acute liver failure; SRSF2 governs splicing of multiple stress-induced cell death pathway genes and acts as a transcription activator required for expression of transcription factors controlling energy homeostasis and bile acid metabolism. Liver-specific conditional knockout mouse (Cre-lox), RNA-seq, histology, biochemical assays Molecular and cellular biology High 27022105
2018 SRSF2P95H mutation globally alters RNA binding (HITS-CLIP) and splicing; most differential binding events do not directly translate to local exon splicing changes, suggesting indirect/cascade effects. SRSF2P95H targets are enriched in RNA processing genes including hnRNP and SR family members; aberrant splicing of HNRNPA2B1 was shown to impair hematopoietic differentiation in vivo. HITS-CLIP, RNA-seq, in vivo hematopoietic differentiation assay Leukemia High 29858584
2018 Conditional knockin mice expressing Srsf2 P95H heterozygously from endogenous locus develop progressive transplantable MDS/MPN with myeloid bias, monocytosis, and dysplasia during native hematopoiesis (no transplant stress); the mutation must occur in HSC-containing populations to promote disease. Conditional knockin mouse (multiple Cre lines), transplantation assay, RNA-seq Blood High 29903888
2019 SRSF2 associates with the P300/CBP acetyltransferase complex and alters H3K27Ac levels near immune checkpoint gene transcription start sites, thereby influencing STAT3 recruitment to these promoters and regulating transcription of multiple immune checkpoint molecules (PD-1, TIM-3, etc.) in exhausted T cells. Co-immunoprecipitation, ChIP for H3K27Ac and STAT3, siRNA knockdown, RT-PCR Cellular and molecular life sciences Medium 31838573
2020 SRSF2 Pro95 hot-spot mutations enhance mRNA decay (NMD) through sequence-specific RNA binding and splicing; mutant SRSF2 enhances deposition of exon junction complexes (EJCs) downstream from PTCs via RNA-mediated molecular interactions, recruiting NMD factors. Antisense oligonucleotide blocking of EJC deposition restores PTC-containing transcript levels. RNA-seq, EJC deposition assays, antisense oligonucleotide rescue, splicing reporter assays Genes & development High 32001512
2020 SFPQ, in complex with p54nrb, binds SRSF2 under platinum treatment and decreases SRSF2 binding to caspase-9 RNA, favoring expression of its antiapoptotic alternatively spliced form and contributing to chemoresistance. Co-immunoprecipitation (SFPQ/p54nrb/SRSF2 complex), RNA immunoprecipitation for caspase-9, siRNA knockdown, RT-PCR for splice isoforms Oncogene Medium 32332923
2023 SRSF2 functions as a reader of m5C RNA modification; structurally identified residues mediate m5C recognition. NSUN2 knockdown decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. The SRSF2P95H leukemia mutation impairs m5C binding and reduces SRSF2 association with key leukemia-related transcripts. m5C-RIP, structural analysis, mutagenesis of m5C-recognition residues, NSUN2 knockdown with RNA-seq, CLIP-seq Molecular cell High 38065062
2024 SRSF2P95H mutation disrupts splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. A mitochondrial surveillance mechanism was identified whereby mitochondrial dysfunction modifies splicing of PINK1 to remove a poison intron, increasing PINK1 mRNA/protein stability and abundance; this increased PINK1-mediated mitophagy is essential for survival of SRSF2P95H/+ cells. RNA-seq for mitochondrial mRNA splicing, mitochondrial complex activity assays, PINK1 splicing reporter, GSK-3 inhibitor treatment, apoptosis assays The Journal of clinical investigation High 38713535
2009 TBX5 associates with SC35 (shown by co-immunoprecipitation and GST pulldown) and competes with SC35 for binding to 5' splice site RNA; co-expression of TBX5 and SC35 antagonizes each other's positive effect on splicing. The severe TBX5 G80R mutation (full cardiac penetrance) strongly affects splicing, linking SC35 interaction to Holt-Oram syndrome pathogenesis. Co-immunoprecipitation, GST pulldown, RNA homopolymer binding assay, minigene splicing assay, site-directed mutagenesis The Journal of biological chemistry Medium 19648116
2008 SC35 (acting through its RRM domain) and ASF/SF2 act antagonistically to regulate growth hormone exon 3 splicing; SC35 acts as a repressor via a site downstream of ESE2, and a patient mutation that creates a functional SC35-binding site causes pathological exon 3 skipping. Chimeric SC35/ASF-SF2 domain swaps, minigene splicing assay, patient mutation analysis The Journal of biological chemistry Medium 18586677
2005 SC35 promotes a shift from primary AChE-S to stress-induced AChE-R splice variant in cotransfection assays, with this activity mapping to the SC35 RRM domain (via chimeric SC35/ASF-SF2 constructs); SC35 levels are elevated in stressed mouse prefrontal cortex coinciding with increased AChE-R mRNA. AChE minigene cotransfection, chimeric RRM/RS domain constructs, RT-PCR, in vivo stress model Molecular psychiatry Medium 16116489
2022 SRSF2 is essential for myogenesis: conditional knockout in Myf5-lineage cells causes complete absence of mature myofibers and neonatal death; SRSF2-null Myf5-derived cells are scattered outside myogenic regions, fail to adopt myogenic fate (shown by lineage tracing), and undergo apoptosis. Conditional knockout (Myf5-Cre), lineage tracing, single-cell RNA-seq, apoptosis assays Advanced science High 35460187

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC genomics 824 17270048
2015 SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition. Cancer cell 503 25965569
1995 The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities. The EMBO journal 317 7543047
2008 The splicing factor SC35 has an active role in transcriptional elongation. Nature structural & molecular biology 304 18641664
2001 SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. The EMBO journal 267 11285241
1992 General splicing factors SF2 and SC35 have equivalent activities in vitro, and both affect alternative 5' and 3' splice site selection. Proceedings of the National Academy of Sciences of the United States of America 230 1454802
1992 Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Science (New York, N.Y.) 229 1373910
1995 Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains. The Journal of cell biology 207 8557734
2015 Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities. Proceedings of the National Academy of Sciences of the United States of America 195 26261309
2000 Exonic splicing enhancer motif recognized by human SC35 under splicing conditions. Molecular and cellular biology 195 10629063
1999 Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific. The Journal of cell biology 172 10037785
2003 Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. The Journal of cell biology 171 12975345
2007 Splicing regulator SC35 is essential for genomic stability and cell proliferation during mammalian organogenesis. Molecular and cellular biology 133 17526736
2001 SC35 plays a role in T cell development and alternative splicing of CD45. Molecular cell 129 11239462
2012 Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PloS one 128 23071587
2012 The clinical implication of SRSF2 mutation in patients with myelodysplastic syndrome and its stability during disease evolution. Blood 126 22932795
2000 Tracking COL1A1 RNA in osteogenesis imperfecta. splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain. The Journal of cell biology 126 10931857
2004 Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. The EMBO journal 124 14963485
2017 SRSF2 Regulates Alternative Splicing to Drive Hepatocellular Carcinoma Development. Cancer research 123 28082404
2011 A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well. The EMBO journal 120 22002536
2003 Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of SC35. Implications for Alzheimer's disease. The Journal of biological chemistry 118 14602710
1995 The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing. Journal of virology 116 7666511
2010 Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. The EMBO journal 113 21157427
2001 CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles. Journal of cell science 113 11683387
1997 Quantitative digital analysis of diffuse and concentrated nuclear distributions of nascent transcripts, SC35 and poly(A). Experimental cell research 100 9056409
2011 DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression. The Journal of biological chemistry 99 22117060
2014 The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression. Cell death & disease 93 25188512
2011 Regulation of the alternative splicing of tau exon 10 by SC35 and Dyrk1A. Nucleic acids research 93 21470964
2008 E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35. Cell death and differentiation 90 18806759
2015 SRSF2 Is Essential for Hematopoiesis, and Its Myelodysplastic Syndrome-Related Mutations Dysregulate Alternative Pre-mRNA Splicing. Molecular and cellular biology 86 26124281
2007 A role for SC35 and hnRNPA1 in the determination of amyloid precursor protein isoforms. Molecular psychiatry 78 17353911
2018 SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells. Leukemia 76 29858584
2017 Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice. Blood 76 29146882
2005 SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA. Molecular psychiatry 74 16116489
2018 The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation. Cell death & disease 72 30375398
2010 The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo. Oncogene 72 20639906
1993 Distribution of snRNPs, splicing factor SC-35 and actin in interphase nuclei: immunocytochemical evidence for differential distribution during changes in functional states. Journal of cell science 71 8408269
2023 SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer. Molecular cell 69 38065062
2005 Dual effect of the SR proteins ASF/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production. Retrovirology 69 15907217
2004 hnRNP A1 and the SR proteins ASF/SF2 and SC35 have antagonistic functions in splicing of beta-tropomyosin exon 6B. The Journal of biological chemistry 69 15208309
2018 Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging 68 30026406
2020 Recurrent SRSF2 mutations in MDS affect both splicing and NMD. Genes & development 67 32001512
2004 Differential effects of the SR proteins 9G8, SC35, ASF/SF2, and SRp40 on the utilization of the A1 to A5 splicing sites of HIV-1 RNA. The Journal of biological chemistry 66 15123677
2009 HSPB7 is a SC35 speckle resident small heat shock protein. Biochimica et biophysica acta 65 19464326
2004 Mimicking phosphorylation of the small heat-shock protein alphaB-crystallin recruits the F-box protein FBX4 to nuclear SC35 speckles. European journal of biochemistry 64 15511225
2013 Mutational analysis of splicing machinery genes SF3B1, U2AF1 and SRSF2 in myelodysplasia and other common tumors. International journal of cancer 61 23280334
2020 Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity. Oncogene 60 32332923
2006 In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains. The Journal of cell biology 59 16431928
2002 Evidence that all SC-35 domains contain mRNAs and that transcripts can be structurally constrained within these domains. Journal of structural biology 57 12490161
2020 Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia. Leukemia 55 32358566
2005 The SR protein SC35 is responsible for aberrant splicing of the E1alpha pyruvate dehydrogenase mRNA in a case of mental retardation with lactic acidosis. Molecular and cellular biology 55 15798212
1997 Transcription-dependent redistribution of nuclear protein 4.1 to SC35-enriched nuclear domains. Journal of cell science 52 9044054
2014 SRSF2-p95 hotspot mutation is highly associated with advanced forms of mastocytosis and mutations in epigenetic regulator genes. Haematologica 50 24389310
2018 Srsf2 initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells. Blood 48 29903888
2015 Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 26508027
2006 Biochemical and NMR study on the competition between proteins SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 at the HIV-1 Tat exon 2 splicing site. The Journal of biological chemistry 45 16990281
2023 HBV Enhances Sorafenib Resistance in Hepatocellular Carcinoma by Reducing Ferroptosis via SRSF2-Mediated Abnormal PCLAF Splicing. International journal of molecular sciences 42 36834680
1994 Several mRNAs with variable 3' untranslated regions and different stability encode the human PR264/SC35 splicing factor. Proceedings of the National Academy of Sciences of the United States of America 42 8302870
2003 Nuclear staining for the small heat shock protein alphaB-crystallin colocalizes with splicing factor SC35. European journal of cell biology 41 12924631
2016 Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in Renal Cancer. International journal of molecular sciences 40 27690003
2009 Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35. The Journal of biological chemistry 40 19648116
2009 Antagonistic factors control the unproductive splicing of SC35 terminal intron. Nucleic acids research 39 19965769
2021 Splicing factor SRSF2-centric gene regulation. International journal of biological sciences 38 33994855
2017 Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia. Oncotarget 38 28209919
2017 A Cytoplasmic RNA Virus Alters the Function of the Cell Splicing Protein SRSF2. Journal of virology 37 28077658
2013 Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories. Cellular and molecular life sciences : CMLS 37 24026398
2016 Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice. Molecular and cellular biology 36 27022105
1997 SC35-mediated reconstitution of splicing in U2AF-depleted nuclear extract. Proceedings of the National Academy of Sciences of the United States of America 36 8990173
2019 Modulation of SRSF2 expression reverses the exhaustion of TILs via the epigenetic regulation of immune checkpoint molecules. Cellular and molecular life sciences : CMLS 34 31838573
2010 Association of adipogenic genes with SC-35 domains during porcine adipogenesis. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 34 21127962
2015 Impact of TET2, SRSF2, ASXL1 and SETBP1 mutations on survival of patients with chronic myelomonocytic leukemia. Experimental hematology & oncology 33 26019984
2013 A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors. Cell cycle (Georgetown, Tex.) 32 23518498
2019 A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells. Scientific reports 31 30674935
2020 Co-mutation pattern, clonal hierarchy, and clone size concur to determine disease phenotype of SRSF2P95-mutated neoplasms. Leukemia 30 33349666
2018 microRNA-mediated regulation of splicing factors SRSF1, SRSF2 and hnRNP A1 in context of their alternatively spliced 3'UTRs. Experimental cell research 30 29331391
1992 The PR264/c-myb connection: expression of a splicing factor modulated by a nuclear protooncogene. Proceedings of the National Academy of Sciences of the United States of America 30 1465383
1998 The expression of the essential nuclear splicing factor SC35 is altered by human immunodeficiency virus infection. Virus research 29 9617768
2016 Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing. Nucleic acids research 28 27507886
2002 WAC, a novel WW domain-containing adapter with a coiled-coil region, is colocalized with splicing factor SC35. Genomics 28 11827461
1998 Characterization of SRp46, a novel human SR splicing factor encoded by a PR264/SC35 retropseudogene. Molecular and cellular biology 28 9671500
2018 Myeloid Disease Mutations of Splicing Factor SRSF2 Cause G2-M Arrest and Skewed Differentiation of Human Hematopoietic Stem and Progenitor Cells. Stem cells (Dayton, Ohio) 27 30004607
2015 Mutations in the Spliceosomal Machinery Genes SRSF2, U2AF1, and ZRSR2 and Response to Decitabine in Myelodysplastic Syndrome. Anticancer research 27 25964599
2011 SRSF2 is required for sodium butyrate-mediated p21(WAF1) induction and premature senescence in human lung carcinoma cell lines. Cell cycle (Georgetown, Tex.) 27 21555914
2008 Growth hormone deficiency and splicing fidelity: two serine/arginine-rich proteins, ASF/SF2 and SC35, act antagonistically. The Journal of biological chemistry 26 18586677
2000 Uterine expression of alternatively spliced mRNAs of mouse splicing factor SC35 during early pregnancy. Molecular human reproduction 25 11101696
2015 HIV-1-Tat Protein Inhibits SC35-mediated Tau Exon 10 Inclusion through Up-regulation of DYRK1A Kinase. The Journal of biological chemistry 24 26534959
2010 Vitamin A metabolite, all-trans-retinoic acid, mediates alternative splicing of protein kinase C deltaVIII (PKCdeltaVIII) isoform via splicing factor SC35. The Journal of biological chemistry 24 20547768
2019 miR-193a-3p Promotes Radio-Resistance of Nasopharyngeal Cancer Cells by Targeting SRSF2 Gene and Hypoxia Signaling Pathway. Medical science monitor basic research 23 30773530
2021 CircPLCE1 facilitates the malignant progression of colorectal cancer by repressing the SRSF2-dependent PLCE1 pre-RNA splicing. Journal of cellular and molecular medicine 22 34173324
2014 SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene. Biochimica et biophysica acta 22 25220236
2011 The structure and selectivity of the SR protein SRSF2 RRM domain with RNA. Nucleic acids research 22 22140111
1997 Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene. Nucleic acids research 22 9358160
2008 Differential dynamics of splicing factor SC35 during the cell cycle. Journal of biosciences 21 19005234
2022 Single-Cell RNA Sequencing Reveals Heterogeneity of Myf5-Derived Cells and Altered Myogenic Fate in the Absence of SRSF2. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 35460187
2011 Splicing factor SC35 promotes tau expression through stabilization of its mRNA. FEBS letters 20 21333649
2009 Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: processing at transcription sites or accumulation in SC35 foci. Cell cycle (Georgetown, Tex.) 20 19177009
1998 Subcellular localization of human immunodeficiency virus type 1 RNAs, Rev, and the splicing factor SC-35. Virology 20 9601515
2024 A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies. The Journal of clinical investigation 19 38713535
2019 SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions? Cancers 19 31426461
2013 SC35 promotes splicing of the C5-V6-C6 isoform of CD44 pre-mRNA. Oncology reports 18 24173428

Missed literature

Know a paper Affinage missed for SRSF2? Flag it for the maintainers and the community.

No submissions yet.