Affinage

SRSF1

Serine/arginine-rich splicing factor 1 · UniProt Q07955

Length
248 aa
Mass
27.7 kDa
Annotated
2026-06-10
100 papers in source corpus 55 papers cited in narrative 55 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRSF1 (SF2/ASF) is a prototypical SR protein that functions as an essential pre-mRNA splicing factor, originally purified as a ~33 kDa activity required for 5' splice site cleavage, lariat formation, and assembly of the earliest prespliceosome complex (PMID:2145194). Its two RRMs recognize purine-rich exonic splicing enhancers and CN motifs through a cooperative, bimodal binding mode, with RRM2 employing a noncanonical surface and the flexible inter-RRM linker permitting RNA engagement on both sides of the RRM2 site (PMID:7543047, PMID:17668007, PMID:33462199); genome-wide binding and positional modeling established that SRSF1 occupancy near the 5' splice site promotes exon inclusion whereas 3'-proximal binding can drive skipping or inclusion (PMID:19116412, PMID:26431027). SRSF1 activity is governed by the phosphorylation state of its RS domain: SRPK1/2 phosphorylate the N-terminal RS region to drive nuclear-speckle assembly and nuclear translocation, Clk/Sty phosphorylates the C-terminal RS region to release it from speckles, and PP1—docked on RRM1—dephosphorylates it, with both phosphorylation and subsequent dephosphorylation being required across the splicing cycle (PMID:9404896, PMID:16209947, PMID:30185622, PMID:33602301); additional control comes from AMPK and Akt phosphorylation within the RRM and from PRMT1-mediated arginine methylation, which together tune RNA binding and splice-target selection (PMID:21045158, PMID:32453427, PMID:37938975). Beyond nuclear splicing, SRSF1 shuttles to the cytoplasm to regulate mRNA stability and translation, including mTORC1-dependent translation, and this shuttling is required for ciliogenesis (PMID:20139984, PMID:34338635); it engages the mRNA export factor NXF1/TAP via its inter-RRM linker, a complex whose assembly depends on SRSF1-stimulated FANCD2 monoubiquitination and which is exploited for pathological C9ORF72 repeat-RNA export (PMID:17668007, PMID:28677678, PMID:38165804). SRSF1 additionally promotes miR-7 maturation via Drosha, stimulates UPF1-dependent nonsense-mediated decay, suppresses R-loop formation to protect genome integrity, and acts as a SUMO pathway regulator interacting with Ubc9 and PIAS1 (PMID:20385090, PMID:29768215, PMID:36759613, PMID:20805487). Acting downstream of MYC, which transcriptionally activates it, SRSF1 is a potent oncoprotein whose overexpression transforms cells through splicing of targets including BIN1, MNK2, S6K1, Ron, caspase-9, and MYO1B and through mTORC1 activation, while it conversely enforces p53-dependent senescence via the RPL5-MDM2 complex and is degraded by the E3 ligase RNF125 (PMID:17310252, PMID:22545246, PMID:18832178, PMID:22245967, PMID:23478443, PMID:37142680). SRSF1 is also essential for T-cell homeostasis and immune tolerance through an SRSF1-PTEN-mTORC1 axis (PMID:31487268). Haploinsufficiency of SRSF1 causes a syndromic neurodevelopmental disorder with a defined DNA methylation episignature (PMID:37071997).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1990 High

    Established SRSF1 as a bona fide splicing factor by showing a purified ~33 kDa protein is necessary and sufficient to reconstitute early spliceosome assembly and 5' splice site usage, defining the core activity all later work builds on.

    Evidence Protein purification to near homogeneity with in vitro splicing complementation and RNA annealing assays in HeLa extracts

    PMID:2145194

    Open questions at the time
    • Did not define the RNA sequence specificity
    • Did not assign roles to individual domains
  2. 1995 High

    Defined the RNA-recognition logic by showing SRSF1's RRMs cooperatively bind a distinct purine-rich motif and that high-affinity sites organized as an exonic splicing enhancer activate splicing, linking sequence recognition to functional splice-site selection.

    Evidence SELEX, full-length binding assays, and in vitro splicing in S100 extracts

    PMID:7543047

    Open questions at the time
    • Structural basis of the cooperative binding not resolved
    • Position-dependent enhancer/silencer effects not yet defined
  3. 1997 High

    Showed that SRSF1 activity is bidirectionally controlled by RS-domain phosphorylation, with phosphorylation needed for assembly and dephosphorylation required for the first catalytic transesterification, framing the protein as a phospho-switch in splicing.

    Evidence In vitro splicing with defined phospho-states and thiophosphorylation to block dephosphorylation

    PMID:9404896

    Open questions at the time
    • Did not identify the responsible kinases and phosphatases
    • Did not connect phospho-state to subcellular localization
  4. 2000 High

    Identified SRPK1 as a direct physiological kinase for SRSF1, showing bacterially co-expressed phosphorylated SRSF1 is soluble and splicing-competent, establishing the upstream enzyme controlling the phospho-switch.

    Evidence Co-expression in E. coli with in vitro splicing and solubility assays

    PMID:10666475

    Open questions at the time
    • Site specificity within the RS domain not mapped
    • Relationship to speckle localization not addressed
  5. 2005 High

    Resolved how sequential kinases partition SRSF1 between subnuclear compartments, showing SRPK1 phosphorylates the N-terminal RS region for speckle assembly and Clk/Sty the C-terminal region for release, mechanistically coupling phosphorylation to localization.

    Evidence SRPK1-SR peptide crystal structure, kinase assays with deletion mutants, and immunofluorescence localization

    PMID:16209947

    Open questions at the time
    • Did not address the opposing phosphatase
    • In vivo consequences of mislocalization not tested
  6. 2007 High

    Defined the structural RNA-binding mode of RRM2 and revealed that the inter-RRM linker is a binding site for the export factor TAP that competes with RNA, providing the first molecular link between SRSF1 and mRNA export.

    Evidence NMR structure of RRM2 with RNA and TAP binding/competition assays

    PMID:17668007

    Open questions at the time
    • Cellular export targets not yet identified
    • RRM1 recognition mode still undefined
  7. 2007 High

    Demonstrated that SRSF1 is an oncoprotein, showing overexpression transforms cells and forms tumors via splicing of BIN1, MNK2, and S6K1, converting a housekeeping splicing factor into a driver of malignancy.

    Evidence Transformation and xenograft assays with shRNA knockdown, RT-PCR splicing, and isoform-rescue epistasis

    PMID:17310252

    Open questions at the time
    • Upstream signals controlling SRSF1 levels in cancer unknown
    • Full target spectrum not defined
  8. 2008 Medium

    Mapped the genome-wide SRSF1 binding landscape, showing thousands of purine-rich sites enriched near splice sites and over-represented on RNA-processing transcripts, scaling the binding logic to the transcriptome.

    Evidence CLIP-seq in HEK cells with motif analysis

    PMID:19116412

    Open questions at the time
    • Did not establish positional rules for inclusion versus skipping
    • Functional consequence of most sites untested
  9. 2008 High

    Connected SRSF1 oncogenesis to a specific signaling output by showing it activates mTORC1 independently of Akt and that this is essential for transformation, linking splicing-factor function to translational control.

    Evidence Phospho-immunoblot, genetic knockdown of mTOR components, and rapamycin in focus-formation and xenograft assays

    PMID:18832178

    Open questions at the time
    • Direct splicing/mRNA target driving mTORC1 not pinpointed
    • Mechanism of Akt bypass unresolved
  10. 2010 High

    Established that SRSF1 negatively autoregulates its own abundance through unproductive splicing coupled to NMD and RRM2/3'UTR-mediated translational repression, and that a miR-7 feedback loop reinforces this, defining how a potent oncoprotein is kept in check.

    Evidence Isoform analysis, polysome fractionation, mutagenesis, Dicer knockdown, RIP, Drosha cleavage and 3'UTR reporter assays

    PMID:20139984 PMID:20385090

    Open questions at the time
    • How feedback is overridden in cancer not resolved here
    • miRNA-independent translational repression mechanism incompletely defined
  11. 2010 High

    Extended SRSF1 function beyond splicing by showing it stimulates global SUMO conjugation via Ubc9 and PIAS1 through its RRM2, identifying a moonlighting role in post-translational modification.

    Evidence Co-IP, knockdown/overexpression, in vitro and in vivo sumoylation, and domain mapping

    PMID:20805487

    Open questions at the time
    • Catalytic basis of E3-like activity not structurally defined
    • Physiological SUMO substrate spectrum incomplete
  12. 2012 High

    Placed SRSF1 in the MYC oncogenic program from both directions, showing MYC transcriptionally activates SRSF1 and that SRSF1 cooperates with MYC to transform cells, establishing a feed-forward oncogenic circuit.

    Evidence ChIP, promoter reporters, MYC/SRSF1 knockdown, orthotopic transplantation, and 3D culture with MKNK2/TEAD1/BIN1/BIM splicing readouts

    PMID:22245967 PMID:22545246

    Open questions at the time
    • Quantitative contribution of each splice target to transformation unclear
    • Tissue specificity of the circuit not mapped
  13. 2012 High

    Revealed a tumor-suppressive arm of SRSF1 by showing it is a necessary component of an RPL5-MDM2 complex that stabilizes p53 and triggers oncogene-induced senescence, explaining a fail-safe against SRSF1-driven transformation.

    Evidence Co-IP of the endogenous complex, p53 stability and senescence assays in primary fibroblasts

    PMID:23478443

    Open questions at the time
    • Splicing-independence of this role not fully delineated
    • How cancers escape this senescence response unresolved
  14. 2015 High

    Resolved long-standing discrepancies by deriving positional rules from transcriptome-wide data, showing 5'-proximal SRSF1 binding favors inclusion while 3'-proximal binding can drive skipping or inclusion, and validated a downstream oncogenic isoform.

    Evidence RNA-seq in 3D culture, de novo motif discovery, Bayesian positional modeling, and CASC4 isoform overexpression

    PMID:26431027

    Open questions at the time
    • Structural basis of position-dependent outcomes not addressed
    • Determinants of skip-versus-include at 3' sites unclear
  15. 2018 High

    Defined two additional post-transcriptional roles, showing SRSF1 stimulates UPF1-dependent NMD downstream of premature termination codons by recruiting UPF1 while bypassing UPF2, broadening its surveillance function.

    Evidence RIP, tethering and NMD reporter assays, and UPF2/EJC depletion

    PMID:29768215

    Open questions at the time
    • Structural basis of UPF1 recruitment unknown
    • Relationship to EJC-dependent NMD not fully separated
  16. 2018 High

    Solved the structural basis for the opposing phosphatase, mapping the PP1 docking surface on RRM1 and showing its disruption lowers RS phosphorylation, redistributes SRSF1 from speckles, and shifts splicing, completing the kinase-phosphatase regulatory circuit.

    Evidence NMR, site-directed mutagenesis, in vitro dephosphorylation, FRAP, and RT-PCR splicing

    PMID:30185622

    Open questions at the time
    • In vivo phenotype of PP1 uncoupling not tested
    • Crosstalk with SRPK/Clk timing unresolved
  17. 2020 High

    Showed that AMPK phosphorylates SRSF1 within the RRM at Ser133 to suppress RNA binding without altering localization, demonstrating that metabolic signaling can directly retune splice-site selection independently of the RS-domain switch.

    Evidence In vitro kinase assay, S133A mutagenesis, RNA-protein interaction and Ron splicing assays

    PMID:32453427

    Open questions at the time
    • Genome-wide consequences of Ser133 phosphorylation untested
    • Physiological metabolic triggers in vivo not defined
  18. 2021 High

    Established that cytoplasmic shuttling of SRSF1 is physiologically required, showing nuclear-retained SRSF1 reduces translation of multiciliogenesis proteins and causes ciliary defects in mice, decoupling its cytoplasmic translational role from nuclear splicing.

    Evidence Nuclear-retention knock-in mouse with developmental phenotyping, polysome/translation assays, proteomics, and cilia EM

    PMID:34338635

    Open questions at the time
    • Specific cytoplasmic mRNA targets driving ciliogenesis not enumerated
    • Mechanism of translational selectivity unclear
  19. 2021 High

    Demonstrated SRSF1 maintains genome integrity by suppressing R-loops, showing hepatocyte deletion causes RNA-DNA hybrid accumulation, DNA damage, and NASH-like pathology, linking its RNA processing role to genome protection in vivo.

    Evidence Hepatocyte-specific Srsf1 knockout mouse with S9.6 R-loop imaging, transcriptome/proteome sequencing, and eCLIP

    PMID:36759613

    Open questions at the time
    • Direct biochemical mechanism of R-loop prevention not defined
    • Contribution of co-factors like RNPS1 not integrated
  20. 2021 High

    Defined a single-molecule, exon-independent recruitment of SRSF1 by U1 snRNP via contacts to U1 snRNA stem-loop 3, providing a mechanistic basis for U1-mediated exon definition beyond enhancer binding.

    Evidence Single-molecule fluorescence with structural cross-linking and stem-loop 3 mutagenesis

    PMID:34779515

    Open questions at the time
    • Generality across endogenous exons not established
    • Interplay with enhancer-dependent recruitment unresolved
  21. 2019 High

    Established SRSF1 as a non-redundant controller of T-cell homeostasis and tolerance, showing T-cell Srsf1 deletion causes autoimmunity via a PTEN-mTORC1 axis rescuable by rapamycin or SRSF1 re-expression.

    Evidence T-cell conditional knockout mice with flow cytometry, PTEN/mTORC1 immunoblots, rapamycin, and overexpression rescue

    PMID:31487268 PMID:32206811 PMID:33863728 PMID:34233194

    Open questions at the time
    • Direct splice/stability targets controlling PTEN not fully mapped
    • Cell-type-specific target sets across T-cell subsets incompletely defined
  22. 2023 High

    Linked SRSF1 dosage to human disease at both extremes, identifying haploinsufficiency as the cause of a syndromic neurodevelopmental disorder with a methylation episignature, while parallel work showed RNF125-mediated degradation and FANCD2-dependent export tie SRSF1 to oncogenic and genome-stability pathways.

    Evidence Drosophila in vivo splicing assays and methylation episignature in patients; Co-IP, ubiquitination, monoubiquitination, and mRNA export/R-loop assays

    PMID:37071997 PMID:37142680 PMID:38165804

    Open questions at the time
    • Genotype-phenotype mechanism of the neurodevelopmental syndrome incompletely defined
    • Structural basis of the SRSF1-FANCD2 interaction unresolved
  23. 2023 High

    Identified PRMT1-mediated arginine methylation as an upstream determinant of SRSF1 phosphorylation, RNA binding, and exon inclusion, adding a methylation layer to the regulatory hierarchy with therapeutic implications in breast cancer.

    Evidence Methylome profiling, in vitro methylation, RNA binding, splicing assays, and pharmacological inhibition with iPRMT1 and SRPK inhibitors

    PMID:37938975

    Open questions at the time
    • Methylated residues' structural impact not resolved
    • Hierarchy with phosphorylation timing not fully ordered

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multilayered modification code (SRPK/Clk phosphorylation, AMPK/Akt RRM phosphorylation, PRMT1 methylation, PP1 dephosphorylation) is integrated in real time to select specific splice, export, decay, and translation targets in a given cell state remains unresolved.
  • No unified model linking modification state to target choice
  • Cell-type-specific target rewiring not mechanistically explained
  • Structural basis of how modifications alter RRM/RS function incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0060090 molecular adaptor activity 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0045182 translation regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
FANCD2NXF1PIAS1PP1RNF125SRPK1UBC9UPF1
Complex memberships
7SK snRNPRPL5-MDM2 complexTREX/UAP56/ALYREF export complexnuclear speckles

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 SF2/ASF (SRSF1) was purified to near homogeneity from HeLa cells as a ~33 kDa protein necessary for 5' splice site cleavage and lariat formation during pre-mRNA splicing in vitro. It is sufficient to complement an S100 fraction for splicing and appears required for assembly or stabilization of the earliest prespliceosome complex. The purified protein also carries RNA annealing activity. Protein purification to near homogeneity; in vitro splicing complementation assay; RNA annealing assay Genes & development High 2145194
1995 SELEX experiments with the RNA-binding domains of ASF/SF2 (SRSF1) and SC35 showed they recognize distinct purine-rich RNA motifs. Full-length protein binding assays confirmed the specificities are distinct and that the charged RS region is not a major specificity determinant for ASF/SF2. Cooperation between the two RBDs of ASF/SF2 determines binding specificity. An exonic splicing enhancer (ESE) containing three copies of a high-affinity ASF/SF2 binding site potently activates splicing in a manner that requires ASF/SF2 plus additional factors in S100 extracts. SELEX (in vitro RNA selection); RNA binding assays with full-length proteins; in vitro splicing assay in S100 extracts The EMBO journal High 7543047
1997 Both phosphorylation and dephosphorylation of ASF/SF2 (SRSF1) are required for pre-mRNA splicing in vitro. Phosphorylated ASF/SF2 complements SR-protein-deficient S100 extracts; unphosphorylated protein inhibits splicing. Thiophosphorylated (non-dephosphorylatable) ASF/SF2 supports spliceosome assembly but blocks the first transesterification reaction, demonstrating that dephosphorylation is required for the catalytic step. In vitro splicing assay; phosphorylation/dephosphorylation of recombinant ASF/SF2; thiophosphorylation to block dephosphorylation RNA (New York, N.Y.) High 9404896
1998 Human DNA topoisomerase I (topo I) phosphorylates SF2/ASF (SRSF1) exclusively within the extended arginine-serine repeats of the RS domain. The N-terminal 174 amino acids of topo I are required for binding SF2/ASF; deletion of this region abolishes both binding and kinase activity. Kinase activity and SF2/ASF binding are tightly coupled; the C-terminal region of topo I contains the ATP-binding site. In vitro kinase assay; far-western blotting; fluorescence spectroscopy; deletion mutagenesis of topo I and SF2/ASF Nucleic acids research High 9611241
1999 The cellular protein p32 was co-purified with ASF/SF2 (SRSF1) and shown to interact directly with ASF/SF2 and SRp30c. p32 inhibits ASF/SF2 function as a splicing enhancer and splicing repressor by preventing stable RNA binding. p32 also inhibits phosphorylation of ASF/SF2 by HeLa nuclear extracts and specific SR kinases, placing p32 as a negative regulator that sequesters ASF/SF2 into an inhibitory complex. Co-purification; in vitro splicing assay; RNA binding assay; in vitro kinase assay The EMBO journal High 10022843
1999 SF2/ASF (SRSF1) controls alternative splicing of CD45 exon 4; its RRM domains (not the RS domain) are required for this skipping activity. Overexpression of SF2 induces CD45 exon 4 skipping in COS cells. SF2 is upregulated during T cell activation, coinciding with a shift from CD45RA to CD45RO isoform expression. Overexpression in COS cells; deletion mutant analysis; T cell activation assays; flow cytometry European journal of immunology Medium 10092085
2000 SRPK1 co-expressed with ASF/SF2 in E. coli phosphorylates ASF/SF2 to a degree resembling native HeLa cell ASF/SF2. The E. coli-phosphorylated ASF/SF2 is functional in splicing and, unlike unphosphorylated protein, is soluble under native conditions, demonstrating that SRPK1 is a direct kinase for SRSF1. Co-expression in E. coli; in vitro splicing assay; protein solubility assay Nucleic acids research High 10666475
2002 ASF/SF2 (SRSF1) inhibits DNA relaxation by human topoisomerase I by interfering with the DNA cleavage and/or DNA binding steps of topoisomerase I catalysis. Inhibition correlates with direct interaction between the RS domain of ASF/SF2 and residues 208–735 of topoisomerase I. Phosphorylation of the RS domain reduces this inhibition. In vitro topoisomerase I relaxation assay; deletion mutant interaction mapping; phosphorylation experiments Journal of molecular biology Medium 12270705
2002 SF2/ASF (SRSF1) inhibits camptothecin-induced DNA cleavage by human topoisomerase I by reducing formation of the cleavable complex; this inhibition is independent of the phosphorylation status of SF2/ASF and does not result from SF2/ASF binding to DNA. In vitro topoisomerase I cleavage assay; camptothecin treatment; phosphorylation controls European journal of biochemistry Medium 12135490
2005 SF2/ASF (SRSF1) directly binds a splicing enhancer in exon 12 of the Ron tyrosine kinase receptor pre-mRNA and controls skipping of exon 11 to generate constitutively active DeltaRon. Overexpression and RNAi of SF2/ASF demonstrate it directly controls epithelial-to-mesenchymal transition and cell motility through DeltaRon isoform production. Knockdown of DeltaRon mRNA reverses the motility effect of SF2/ASF overexpression. RNA binding assay; overexpression and RNAi; RT-PCR splicing assay; cell motility assay; epistasis by DeltaRon knockdown Molecular cell High 16364913
2005 Crystal structure of SRPK1 bound to an SR-protein peptide identified a docking motif in ASF/SF2 (SRSF1). This docking motif restricts SRPK1-mediated phosphorylation to the N-terminal portion of the RS domain, which is essential for assembly of ASF/SF2 into nuclear speckles. Clk/Sty kinase subsequently phosphorylates the C-terminal portion of the RS domain, causing release of ASF/SF2 from speckles. Sequential phosphorylation by SRPK1 then Clk/Sty thus controls subcellular localization. Crystal structure; in vitro kinase assay with deletion mutants; subcellular localization by immunofluorescence; docking motif mutagenesis Molecular cell High 16209947
2006 SRp30a (SRSF1) regulates the alternative splicing of caspase-9 pre-mRNA: its downregulation by RNAi increases the antiapoptotic caspase-9b isoform and decreases the proapoptotic caspase-9a isoform. SRp30a is also required for ceramide to induce inclusion of the exon 3/4/5/6 cassette of caspase-9. RNAi knockdown; RT-PCR splicing assay; ceramide treatment Journal of lipid research Medium 16505493
2007 NMR structure of RRM2 of SF2/ASF (SRSF1) revealed that RRM2 binds RNA using a conserved SWQLKD tryptophan on helix α1 combined with strand β2 residues and a histidine on loop 5 — a novel RNA-binding mode. The linker connecting RRM1 and RRM2 contains arginine residues that form a binding site for the mRNA export factor TAP; TAP binding to this linker displaces RNA bound to RRM2. NMR structure determination; RNA binding assay; TAP binding assay with competition experiment EMBO reports High 17668007
2007 SF2/ASF (SRSF1) overexpression transforms immortal rodent fibroblasts that form sarcomas in nude mice; transformation is driven in part by alternative splicing of BIN1 (generating isoforms lacking tumor-suppressor activity), MNK2 (producing an isoform with MAP kinase-independent eIF4E phosphorylation), and S6K1 (producing an oncogenic isoform). Knockdown of SF2/ASF or the oncogenic S6K1 isoform reverses transformation in vitro and in vivo. Overexpression transformation assay; nude mouse xenograft; shRNA knockdown; RT-PCR splicing; epistasis by S6K1 isoform knockdown Nature structural & molecular biology High 17310252
2008 CLIP-seq of SFRS1 (SRSF1) in human embryonic kidney cells identified 23,632 binding sites across diverse RNA classes (mRNA, miRNA, snoRNA, ncRNA) sharing a purine-rich consensus motif. SFRS1-bound sequences are enriched near splice sites. mRNAs encoding RNA processing factors are significantly over-represented among SFRS1 targets. CLIP-seq (cross-linking immunoprecipitation and high-throughput sequencing); motif analysis Genome research Medium 19116412
2008 SF2/ASF (SRSF1) overexpression activates the mTORC1 branch of the mTOR pathway, measured by S6K and 4EBP1 phosphorylation, without activating Akt (mTORC2 substrate). mTORC1 activation bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF-mediated transformation; rapamycin blocks transformation in vitro and in vivo. Phosphorylation immunoblot; shRNA knockdown of mTOR, Raptor, Rictor; rapamycin inhibition; focus formation and xenograft assay Proceedings of the National Academy of Sciences of the United States of America High 18832178
2010 SF2/ASF (SRSF1) negatively autoregulates its own expression through multiple post-transcriptional and translational mechanisms. Unproductive alternative splicing (generating NMD-sensitive isoforms) accounts for part of the autoregulation. The primary mechanism is translational repression mediated by RRM2 and the ultraconserved 3'UTR. Overexpression shifts the target mRNA toward monoribosomes. Translational repression is partly independent of Dicer and 5' cap. RT-PCR isoform analysis; polysome fractionation; mutagenesis of RRM2 and 3'UTR; Dicer knockdown Nature structural & molecular biology High 20139984
2010 SF2/ASF (SRSF1) directly interacts with the primary miR-7 transcript (pri-miR-7) to facilitate Drosha cleavage, promoting miR-7 maturation independently of its splicing function. Mature miR-7 in turn targets the 3'UTR of SF2/ASF to repress its translation, forming a negative feedback loop. Similar regulation may apply to miR-221 and miR-222. miRNA deep sequencing; RNA immunoprecipitation; Drosha cleavage assay; 3'UTR reporter assay; overexpression and knockdown Molecular cell High 20385090
2010 SF2/ASF (SRSF1) is a regulator of the SUMO conjugation pathway: overexpression stimulates and knockdown inhibits global SUMO conjugation. SRSF1 interacts with the SUMO E2 enzyme Ubc9 and the E3 ligase PIAS1, and RRM2 is necessary and sufficient for sumoylation enhancement. SRSF1 promotes sumoylation of RNA processing factors and is involved in heat-shock-induced sumoylation. Co-immunoprecipitation; overexpression and knockdown; in vitro and in vivo sumoylation assay; domain deletion analysis Proceedings of the National Academy of Sciences of the United States of America High 20805487
2010 SRSF1 overexpression in NSCLC cells promotes survival by binding survivin mRNA, enhancing its translation through an mTORC1/4E-BP1-dependent mechanism, and increasing survivin mRNA stability. SRSF1 knockdown reduces survivin protein and induces apoptosis. RNA immunoprecipitation; mTORC1 inhibition (rapamycin); siRNA knockdown; western blot; mRNA stability assay Clinical cancer research Medium 20682707
2010 Akt phosphorylates SRSF1 (SRp30a) at serines 199, 201, 227, and 234 via the PI3K/Akt pathway, mediating exclusion of the exon 3/4/5/6 cassette of caspase-9 pre-mRNA to produce antiapoptotic caspase-9b in NSCLC cells. PI3K/Akt inhibition; phosphorylation mapping by site-directed mutagenesis; RT-PCR splicing assay; EGFR overexpression/mutation models Cancer research Medium 21045158
2011 SRSF1 is hyperphosphorylated in response to chronic replication-dependent DNA damage (ATM activation) in 46BR.1G1 cells; this hyperphosphorylation is partially prevented by ATM inhibitor caffeine. Hyperphosphorylation of SRSF1 alters its subnuclear distribution and shifts the alternative splicing of target genes. Proteomic phosphorylation analysis; ATM inhibition; immunofluorescence subnuclear localization; RT-PCR splicing assay Nucleic acids research Medium 21984412
2012 SRSF1 overexpression in mammary epithelial cells promotes alternative splicing of BIM and BIN1 to generate isoforms lacking pro-apoptotic functions, contributing to increased proliferation and delayed apoptosis. These oncogenic effects require RRM1 and nuclear functions of SRSF1. SRSF1 cooperates specifically with MYC to transform mammary epithelial cells, in part by potentiating eIF4E activation. Overexpression in MCF-10A and COMMA-1D cells; orthotopic transplantation; 3D culture; RT-PCR splicing; domain deletion analysis; MYC co-expression Nature structural & molecular biology High 22245967
2012 MYC directly activates transcription of SRSF1 through two non-canonical E-boxes in its promoter. Increased SRSF1 downstream of MYC is sufficient to modulate alternative splicing of MKNK2 and TEAD1. SRSF1 knockdown reduces MYC oncogenic activity (proliferation, anchorage-independent growth). Chromatin immunoprecipitation (ChIP); promoter reporter assay; MYC knockdown; SRSF1 knockdown; RT-PCR splicing assay Cell reports High 22545246
2012 SRSF1 is a necessary component of an MDM2/RPL5 ribosomal protein complex (separate from the ribosome) that stabilizes p53 by abrogating MDM2-dependent proteasomal degradation. Increased SRSF1 expression in primary human fibroblasts induces p53-dependent oncogene-induced senescence (OIS), implicating RPL5-MDM2 complex in OIS. Co-immunoprecipitation; p53 stability assay; SRSF1 overexpression in primary fibroblasts; senescence assays (SA-β-gal); MDM2 inhibition controls Molecular cell High 23478443
2012 SRSF1 depletion in human cells compromises association of splicing factors with nuclear speckles and influences levels/activity of other SR proteins. SRSF1, together with lncRNA MALAT1, can nucleate assembly of nuclear speckles. On a stably integrated reporter gene locus, SRSF1 promotes RNA Pol II-mediated transcription. siRNA knockdown; immunofluorescence of nuclear speckle markers; reporter gene assay with stable integration; FRAP-like analysis Molecular biology of the cell Medium 22855529
2013 SRSF1 directly controls alternative splicing of fibronectin EDA exon inclusion in human primary endometrial fibroblasts; RNAi knockdown of SRSF1 reduces EDA+ fibronectin, and higher SRSF1 expression in endometrium is linked to stronger EDA exon inclusion and consequently greater trophoblast invasion capacity in co-culture assay. RNAi; RT-PCR splicing assay; co-culture invasion assay; quantitative protein expression analysis Molecular biology of the cell Medium 23966470
2014 HIV-1 transcription factor SRSF1 and Tat recognize overlapping sequences within TAR RNA and 7SK RNA. SRSF1 can increase basal HIV-1 transcription in the absence of Tat by recruiting P-TEFb to TAR from the 7SK snRNP, and can inhibit Tat transactivation by directly competing for TAR binding. RNA binding competition assay; Tat transactivation reporter assay; co-immunoprecipitation with 7SK snRNP components; overexpression/knockdown Nucleic acids research Medium 25416801
2014 SRSF1 binds to CD6 intron 4 and activates exon 5 splicing (promoting exon 5 inclusion). During T cell activation, SRSF1 levels decrease, its recruitment to the CD6 transcript is impaired by increased chromatin acetylation, and this leads to exon 5 skipping generating CD6Δd3, which no longer localizes at the immunological synapse. RNA immunoprecipitation; chromatin immunoprecipitation; HDAC inhibitor treatment; overexpression/knockdown; RT-PCR Journal of immunology Medium 24890719
2015 RNA-seq in 3D MCF-10A cultures identified hundreds of SRSF1-regulated alternative splicing events. De novo motif discovery reconciled previous discrepancies. Bayesian positional modeling showed that SRSF1 binding near the 5' splice site generally promotes exon inclusion, whereas binding near the 3' splice site promotes either skipping or inclusion. Overexpression of an SRSF1-regulated exon-9-included CASC4 isoform partially recapitulates SRSF1's oncogenic effects. RNA-seq; de novo motif discovery; Bayesian positional model; RT-PCR validation; CASC4 isoform overexpression in 3D culture Molecular cell High 26431027
2017 SRSF1 promotes vascular smooth muscle cell (VSMC) proliferation by favoring production of the truncated p53 isoform Δ133p53. Δ133p53 transcriptionally activates KLF5 via a Δ133p53-EGR1 complex, accelerating cell-cycle progression. SMC-specific Srsf1 knockout mice develop less intimal thickening after wire injury, and Srsf1 overexpression in rat arteries enhances neointima formation. Conditional SMC-specific knockout mouse; wire injury model; adenoviral overexpression; immunoprecipitation of Δ133p53-EGR1 complex; siRNA knockdown; cell proliferation assay Nature communications High 28799539
2017 Depletion of SRSF1 specifically prevents nuclear export of pathological C9ORF72 repeat-containing transcripts via the NXF1 pathway, suppressing dipeptide repeat protein production and neurodegeneration in Drosophila and patient-derived neurons. Preventing the interaction of SRSF1 with NXF1 also inhibits this export and alleviates neurotoxicity. SRSF1 depletion in Drosophila (genetic); patient-derived motor neuron co-culture; SRSF1-NXF1 interaction disruption; nuclear/cytoplasmic fractionation; repeat RNA export assay Nature communications High 28677678
2018 SRSF1 stimulates nonsense-mediated mRNA decay (NMD) by increasing UPF1 binding to mRNAs while in or associated with the nucleus, bypassing UPF2 recruitment. SRSF1 acts downstream of a PTC in a manner analogous to the EJC, and splicing/EJC deposition enhances the SRSF1-mediated NMD effect. RNA immunoprecipitation; tethering assay; NMD reporter assay; UPF2 depletion; EJC depletion; endogenous PTC-containing transcript analysis Cell reports High 29768215
2018 SRSF1 binds to LIG1 mRNA and regulates LIG1 expression by increasing mRNA stability and enhancing translation in an mTOR-dependent manner in NSCLC cells. RNA immunoprecipitation; mRNA stability assay; mTOR inhibition (rapamycin); siRNA knockdown; western blot Laboratory investigation Medium 30181552
2018 NMR spectroscopy identified two electrostatic residues in helix α2 and a hydrophobic residue in helix α1 of RRM1 of SRSF1 as the binding surface for protein phosphatase 1 (PP1). Mutations in these residues dissociate SRSF1 from PP1, enhance phosphatase activity, reduce RS domain phosphorylation, shift alternative splicing patterns, and increase SRSF1 diffusion from speckles to the nucleoplasm. NMR spectroscopy; site-directed mutagenesis; in vitro dephosphorylation assay; FRAP (diffusion from speckles); RT-PCR splicing assay The Journal of biological chemistry High 30185622
2019 SRSF1 controls alternative splicing of MYO1B to produce membrane-localized oncogenic MYO1B-fl isoform in glioma. SRSF1-guided AS of MYO1B activates PDK1/AKT and PAK/LIMK pathways to promote cell proliferation, survival, and invasion. RNA-seq; RT-PCR splicing assay; siRNA knockdown; MYO1B-fl overexpression; pathway inhibition; xenograft model The Journal of clinical investigation High 30481162
2019 T cell-restricted Srsf1-deficient mice develop systemic autoimmunity; T cells show reduced PTEN expression and increased mTORC1 activity. mTORC1 inhibitor rapamycin suppresses proinflammatory cytokine production and autoimmunity in Srsf1-deficient mice. SRSF1 overexpression restores PTEN and suppresses mTORC1 activation, establishing an SRSF1–PTEN–mTORC1 axis in T cells. T cell-conditional Srsf1 knockout mouse; flow cytometry; immunoblot of PTEN and mTORC1 targets; rapamycin treatment; SRSF1 overexpression rescue The Journal of clinical investigation High 31487268
2020 AMP-activated protein kinase (AMPK) directly phosphorylates SRSF1 at Ser133 within RRM. Ser133 phosphorylation suppresses SRSF1 interaction with specific RNA sequences without altering subcellular localization, and AMPK-dependent phosphorylation of SRSF1 regulates alternative splicing of Ron pre-mRNA by suppressing SRSF1 binding to exon 12. In vitro kinase assay; site-directed mutagenesis (S133A); RNA-protein interaction assay; RT-PCR splicing assay; subcellular fractionation The Biochemical journal High 32453427
2021 NMR and structural analysis of SRSF1 RRM1 revealed that it binds preferentially to a CN motif (C followed by any nucleotide). The flexible inter-RRM linker allows RRM1 to bind RNA on both sides of the RRM2 binding site (bimodal interaction mode). An E87N mutation in RRM1 engineered from this structure enables binding to uridines and activates SMN exon 7 inclusion. NMR structure determination; RNA binding assay; site-directed mutagenesis (E87N); splicing assay (SMN exon 7 inclusion) Nature communications High 33462199
2021 SRSF1 depletion prevents R-loop formation in hepatocytes; SRSF1 loss causes excessive RNA-DNA hybrids, induces DNA damage, globally inhibits mRNA transcription and protein synthesis, impairs lipid metabolism/trafficking, and leads to necroptotic cell death with NASH-like liver pathology in mice. These effects are reproduced in SRSF1-depleted human liver cancer cells. Hepatocyte-specific conditional Srsf1 knockout mouse; R-loop immunofluorescence (S9.6 antibody); transcriptome and proteome sequencing; RNA binding analysis (eCLIP); liver pathology Nature communications High 36759613
2021 SRSF1 nuclear retention (via knock-in NRS) in mice causes small body size, hydrocephalus, and immotile sperm due to ciliary defects. Nuclear-retained SRSF1 reduces translation of a subset of mRNAs and decreases abundance of proteins involved in multiciliogenesis, disrupting ciliary ultrastructure and motility, demonstrating that cytoplasmic shuttling of SRSF1 is required for ciliogenesis. Genome editing (knock-in NRS); mouse developmental phenotyping; polysome/translation assay; proteomics; electron microscopy of cilia eLife High 34338635
2021 A single molecule of SRSF1 can be recruited by a U1 snRNP independently of exon sequences. Structural and cross-linking data show SRSF1 contacts U1 snRNA stem-loop 3. This exon-independent recruitment is proposed to underlie exon definition by U1 snRNP. Single-molecule fluorescence; structural NMR/cross-linking analysis; mutagenesis of stem-loop 3 The EMBO journal High 34779515
2021 SRSF1 conditional deletion in T cells causes T cell lymphopenia with increased apoptosis and decreased expression of anti-apoptotic Bcl-xL. SRSF1 overexpression rescues T cell survival from SLE patients, establishing a direct role for SRSF1 in controlling Bcl-xL expression and T cell homeostasis. Conditional Srsf1 KO mouse; flow cytometry (apoptosis); quantitative PCR and immunoblot of Bcl-xL; SRSF1 overexpression rescue in human T cells Rheumatology (Oxford, England) Medium 32206811
2021 SRSF1 inhibits autophagosome formation by (1) promoting splicing of Bcl-xL long isoform which binds Beclin1 and dissociates the Beclin1-PIK3C3 complex, and (2) directly interacting with PIK3C3 to disrupt Beclin1-PIK3C3 interaction. SRSF1 itself is degraded by starvation/oxidative stress-induced autophagy through interaction with LC3-II, creating a positive feedback loop. Co-immunoprecipitation; siRNA knockdown; LC3-II autophagy markers; RT-PCR splicing assay; starvation and oxidative stress assays; xenograft model Signal transduction and targeted therapy High 33664238
2021 SRSF1 directly binds MALAT1 lncRNA and facilitates its RNA stability in glioma cells. SRSF1 is the most highly expressed SRSF in 9 tumor types, and it regulates the cell cycle in glioma by stabilizing NEAT1 lncRNA through direct binding. RNA immunoprecipitation; RNA stability assay; SRSF1 knockdown; NEAT1 knockdown cell cycle analysis The international journal of biochemistry & cell biology Medium 31200124
2021 SRSF1 directly binds and promotes export of NKILA lncRNA via clustered SRSF1/SRSF7 binding sites in CAR-N region, facilitating TREX/UAP56/ALYREF assembly and TAP-dependent nuclear export; NKILA lacking CAR-N is unable to inhibit breast cancer cell migration. RNA pull-down; mass spectrometry; siRNA screening; EMSA; RNA and protein immunoprecipitation; knock-in models Nucleic acids research Medium 34096602
2021 SRPK1/2 phosphorylate SRSF1, promoting its nuclear translocation, and PP1α opposes this by dephosphorylating SRSF1. The balance of SRSF1 phosphorylation/subcellular localization by SRPK1/2 and PP1α controls alternative splicing of MKNK2 in colon adenocarcinoma cells, with high nuclear SRSF1 promoting MKNK2b (oncogenic) isoform. Immunohistochemistry; western blot; siRNA knockdown; RT-PCR splicing assay; xenograft model; phosphorylation analysis Journal of experimental & clinical cancer research Medium 33602301
2021 SRSF1 conditional deletion in thymocytes blocks the transition of immature TCRβhi thymocytes to mature ones. SRSF1 directly binds and regulates alternative splicing of Irf7 and Il27ra in response to type I interferon signaling; forced IRF7 expression rectifies the maturation defects of SRSF1-deficient thymocytes. Conditional Srsf1 KO mouse; flow cytometry; RNA-seq; SRSF1-RNA binding assay; IRF7 rescue overexpression Science advances High 33863728
2021 Conditional deletion of SRSF1 in Treg cells causes profound autoimmunity; mechanistically, loss of SRSF1 elevates glycolytic metabolism and mTORC1 activity, and increases proinflammatory cytokine production, controlling Treg cell plasticity. Treg-specific Srsf1 conditional KO mouse; flow cytometry; metabolic assays (glycolysis); mTORC1 pathway immunoblot; cytokine measurement Cell reports Medium 34233194
2021 The RNA binding protein RNPS1, when overexpressed, suppresses DNA fragmentation, hypermutation, and G2 arrest caused by ASF/SF2 (SRSF1) depletion. This suggests RNPS1 functions together with ASF/SF2 to form RNP complexes on nascent transcripts and prevent R-loop formation; ASF/SF2 depletion does not affect RNPS1 expression, and RNPS1 cannot compensate for ASF/SF2 splicing function. RNAi depletion; RNPS1 overexpression suppressor experiment; DNA damage assays (HMW fragmentation, mutation frequency); cell cycle analysis RNA (New York, N.Y.) Medium 17959926
2023 PRMT1 methylates SRSF1; this methylation is critical for SRSF1 phosphorylation, SRSF1 binding to RNA, and exon inclusion. PRMT1 overexpression in breast tumors correlates with increased SRSF1 arginine methylation and aberrant exon inclusion. A selective PRMT1 inhibitor (iPRMT1) suppresses SRSF1 methylation, exon inclusion, and breast cancer cell growth; combination with SRSF1 phosphorylation inhibitors shows additive growth suppression. PRMT1 methylome profiling; in vitro methylation assay; RNA binding assay; RT-PCR splicing; pharmacological inhibition (iPRMT1, SRPK inhibitor); cell proliferation assay Cell reports High 37938975
2023 SRSF1 activates MAPK signaling in pancreas by upregulating IL1R1 through alternative-splicing-regulated mRNA stability. In phenotypically normal epithelial cells expressing KRASG12D, SRSF1 protein is destabilized through a negative feedback mechanism. Hyperactive MYC overcomes this feedback, facilitating PDAC tumorigenesis. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Conditional transgenic/KO mouse models; pancreas organoids; RNA-seq; RT-PCR; mRNA stability assay; MAPK pathway immunoblot Cancer discovery High 37098965
2023 Haploinsufficiency of SRSF1 causes a syndromic neurodevelopmental disorder. Loss-of-function and pathogenic missense variants impair SRSF1 splicing activity as demonstrated by in vivo splicing assay in Drosophila, and correlate with a detectable DNA methylation episignature in blood-derived DNA from affected individuals. In vivo Drosophila splicing assay; in silico structural modeling; DNA methylation episignature analysis; genotype-phenotype analysis in 17 individuals American journal of human genetics Medium 37071997
2023 RNF125 E3 ubiquitin ligase physically interacts with SRSF1 (identified by mass spectrometry and co-immunoprecipitation) and accelerates proteasome-mediated degradation of SRSF1, thereby inhibiting the SRSF1/ERK signaling pathway and suppressing HCC proliferation and metastasis. Mass spectrometry; co-immunoprecipitation; ubiquitin ladder assay; proteasome inhibition; siRNA/overexpression; xenograft model Oncogene Medium 37142680
2024 SRSF1 physically interacts with FANCD2 (identified by Co-IP); SRSF1 stimulates FANCD2 monoubiquitination in an RNA-dependent fashion. FANCD2 monoubiquitination is required for assembly of the SRSF1-NXF1 nuclear export complex and mRNA export. Cancer-associated SRSF1 mutants fail to interact with FANCD2, leading to deficient FANCD2 monoubiquitination, decreased mRNA export, and R-loop accumulation. Co-immunoprecipitation; monoubiquitination assay; mRNA export assay; R-loop detection (S9.6); SRSF1 cancer mutant analysis Cell reports High 38165804

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 SF1 and SF2 helicases: family matters. Current opinion in structural biology 766 20456941
2007 The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nature structural & molecular biology 761 17310252
2012 The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nature structural & molecular biology 364 22245967
1990 Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes & development 327 2145194
2005 Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Molecular cell 320 16364913
1995 The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities. The EMBO journal 317 7543047
2016 Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation. Cancer research 268 27993818
2015 SRSF1-Regulated Alternative Splicing in Breast Cancer. Molecular cell 268 26431027
2008 Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome research 256 19116412
2014 Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Molecular cancer research : MCR 233 24807918
2005 Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. Molecular cell 178 16209947
2016 Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer. PLoS genetics 176 27093186
2012 Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC. Cell reports 172 22545246
2010 SF2/ASF autoregulation involves multiple layers of post-transcriptional and translational control. Nature structural & molecular biology 164 20139984
1997 Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro. RNA (New York, N.Y.) 164 9404896
2010 A splicing-independent function of SF2/ASF in microRNA processing. Molecular cell 160 20385090
2014 MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 148 24857172
1999 The splicing factor-associated protein, p32, regulates RNA splicing by inhibiting ASF/SF2 RNA binding and phosphorylation. The EMBO journal 144 10022843
2019 Splicing factor SRSF1 promotes gliomagenesis via oncogenic splice-switching of MYO1B. The Journal of clinical investigation 123 30481162
2010 Alternative splicing of caspase 9 is modulated by the phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. Cancer research 113 21045158
2012 SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles. Molecular biology of the cell 110 22855529
2017 SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature communications 107 28677678
2008 The splicing-factor oncoprotein SF2/ASF activates mTORC1. Proceedings of the National Academy of Sciences of the United States of America 106 18832178
2014 Mutual inhibition between YAP and SRSF1 maintains long non-coding RNA, Malat1-induced tumourigenesis in liver cancer. Cellular signalling 102 24468535
2013 SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing β-catenin biosynthesis. EMBO molecular medicine 101 23592547
2021 SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer. Signal transduction and targeted therapy 98 33664238
2010 MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF). The Journal of biological chemistry 97 21118818
2018 SRSF1 modulates PTPMT1 alternative splicing to regulate lung cancer cell radioresistance. EBioMedicine 93 30429088
2013 Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence. Molecular cell 93 23478443
2017 SRSF1 promotes vascular smooth muscle cell proliferation through a Δ133p53/EGR1/KLF5 pathway. Nature communications 84 28799539
2012 Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. PloS one 78 23284704
1998 Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor. Nucleic acids research 75 9611241
2021 SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma. Journal of experimental & clinical cancer research : CR 70 33602301
2019 Splicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity. The Journal of clinical investigation 70 31487268
2007 Structural and functional analysis of RNA and TAP binding to SF2/ASF. EMBO reports 66 17668007
2006 SRp30a (ASF/SF2) regulates the alternative splicing of caspase-9 pre-mRNA and is required for ceramide-responsiveness. Journal of lipid research 64 16505493
2017 SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing. Cell reports 63 29262322
2018 Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1. Cell reports 61 29768215
2006 Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef. Virology 60 16916529
2023 Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer. Cancer discovery 59 37098965
1999 SF2 and SRp55 regulation of CD45 exon 4 skipping during T cell activation. European journal of immunology 59 10092085
2022 Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop. Molecular cancer 56 36199071
2016 Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells. Oncotarget 56 26887056
2022 METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in prostate cancer via SRSF1/c-Myc axis. Experimental cell research 54 35405116
2021 Extracellular matrix stiffness controls VEGF165 secretion and neuroblastoma angiogenesis via the YAP/RUNX2/SRSF1 axis. Angiogenesis 54 34170441
2012 Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia. Journal of hematology & oncology 53 22839530
2010 The serine/arginine-rich protein SF2/ASF regulates protein sumoylation. Proceedings of the National Academy of Sciences of the United States of America 53 20805487
2007 The RNA binding protein RNPS1 alleviates ASF/SF2 depletion-induced genomic instability. RNA (New York, N.Y.) 53 17959926
2017 DNA-methylation-mediated repression of miR-766-3p promotes cell proliferation via targeting SF2 expression in renal cell carcinoma. International journal of cancer 50 28657135
2015 Posttranscriptional Regulation of Splicing Factor SRSF1 and Its Role in Cancer Cell Biology. BioMed research international 48 26273603
2021 Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing. Nature communications 47 33462199
2010 The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression. Clinical cancer research : an official journal of the American Association for Cancer Research 47 20682707
2019 The RNA-binding protein SRSF1 is a key cell cycle regulator via stabilizing NEAT1 in glioma. The international journal of biochemistry & cell biology 46 31200124
2014 HIV-1 transcription is regulated by splicing factor SRSF1. Nucleic acids research 42 25416801
2023 Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death. Nature communications 41 36759613
2021 Long noncoding RNA DGCR5 involves in tumorigenesis of esophageal squamous cell carcinoma via SRSF1-mediated alternative splicing of Mcl-1. Cell death & disease 41 34099633
2019 Long non-coding RNA MIR205HG regulates KRT17 and tumor processes in cervical cancer via interaction with SRSF1. Experimental and molecular pathology 41 31655037
2009 The hepatitis delta virus RNA genome interacts with eEF1A1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2. Virology 40 19464723
2021 Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function. eLife 37 34338635
2018 The oncogenic RNA-binding protein SRSF1 regulates LIG1 in non-small cell lung cancer. Laboratory investigation; a journal of technical methods and pathology 37 30181552
2021 SRSF1 serves as a critical posttranscriptional regulator at the late stage of thymocyte development. Science advances 36 33863728
2020 SRSF1 regulates exosome microRNA enrichment in human cancer cells. Cell communication and signaling : CCS 36 32819370
2020 Splicing factor SRSF1 controls T cell homeostasis and its decreased levels are linked to lymphopenia in systemic lupus erythematosus. Rheumatology (Oxford, England) 34 32206811
2021 Exon-independent recruitment of SRSF1 is mediated by U1 snRNP stem-loop 3. The EMBO journal 33 34779515
2021 Splicing factor SRSF1 is indispensable for regulatory T cell homeostasis and function. Cell reports 32 34233194
2023 Targeting PRMT1-mediated SRSF1 methylation to suppress oncogenic exon inclusion events and breast tumorigenesis. Cell reports 31 37938975
2022 circSLC41A1 Resists Porcine Granulosa Cell Apoptosis and Follicular Atresia by Promoting SRSF1 through miR-9820-5p Sponging. International journal of molecular sciences 31 35163432
2011 Phosphorylation of SRSF1 is modulated by replicational stress. Nucleic acids research 31 21984412
2014 T cell activation regulates CD6 alternative splicing by transcription dynamics and SRSF1. Journal of immunology (Baltimore, Md. : 1950) 30 24890719
2024 The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export. Cell reports 29 38165804
2015 XPB: An unconventional SF2 DNA helicase. Progress in biophysics and molecular biology 28 25641424
2023 SRSF1 inhibits ferroptosis and reduces cisplatin chemosensitivity of triple-negative breast cancer cells through the circSEPT9/GCH1 axis. Journal of proteomics 27 38040194
2019 SRSF1-dependent alternative splicing attenuates BIN1 expression in non-small cell lung cancer. Journal of cellular biochemistry 27 31478261
2013 Structure and Mechanisms of SF2 DNA Helicases. Advances in experimental medicine and biology 27 23161006
2020 SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid leukemia. Leukemia 26 32051529
2011 Predicting sequence and structural specificities of RNA binding regions recognized by splicing factor SRSF1. BMC genomics 26 22369183
2000 Functional coexpression of serine protein kinase SRPK1 and its substrate ASF/SF2 in Escherichia coli. Nucleic acids research 26 10666475
2021 CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma. Journal of translational medicine 25 34001131
2021 SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular neurodegeneration 25 34376242
2021 Sequence-dependent recruitment of SRSF1 and SRSF7 to intronless lncRNA NKILA promotes nuclear export via the TREX/TAP pathway. Nucleic acids research 24 34096602
2018 Molecular interactions connecting the function of the serine-arginine-rich protein SRSF1 to protein phosphatase 1. The Journal of biological chemistry 24 30185622
2002 The RNA splicing factor ASF/SF2 inhibits human topoisomerase I mediated DNA relaxation. Journal of molecular biology 24 12270705
2021 Splicing factor SRSF1 limits IFN-γ production via RhoH and ameliorates experimental nephritis. Rheumatology (Oxford, England) 23 32810232
2021 LINC00857 regulated by ZNF460 enhances the expression of CLDN12 by sponging miR-150-5p and recruiting SRSF1 for alternative splicing to promote epithelial-mesenchymal transformation of pancreatic adenocarcinoma cells. RNA biology 23 35442145
2023 Targeting alternative splicing as a new cancer immunotherapy-phosphorylation of serine arginine-rich splicing factor (SRSF1) by SR protein kinase 1 (SRPK1) regulates alternative splicing of PD1 to generate a soluble antagonistic isoform that prevents T cell exhaustion. Cancer immunology, immunotherapy : CII 22 37973660
2021 lncRNA LINC01296 Promotes Oral Squamous Cell Carcinoma Development by Binding with SRSF1. BioMed research international 22 34195277
2022 USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1. Cell death discovery 21 35027535
2021 Propofol suppresses colorectal cancer development by the circ-PABPN1/miR-638/SRSF1 axis. Analytical biochemistry 21 34453920
2020 Splicing Factor SRSF1 Is Essential for Satellite Cell Proliferation and Postnatal Maturation of Neuromuscular Junctions in Mice. Stem cell reports 21 32888503
2023 SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability. American journal of human genetics 20 37071997
2020 AMP-activated protein kinase regulates alternative pre-mRNA splicing by phosphorylation of SRSF1. The Biochemical journal 20 32453427
2013 Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein that controls host cell invasion. Molecular biology of the cell 20 23966470
2016 Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis. Oncotarget 19 27363031
2002 SF2/ASF protein inhibits camptothecin-induced DNA cleavage by human topoisomerase I. European journal of biochemistry 19 12135490
2023 RNF125 attenuates hepatocellular carcinoma progression by downregulating SRSF1-ERK pathway. Oncogene 18 37142680
2023 SRSF1 regulates primordial follicle formation and number determination during meiotic prophase I. BMC biology 17 36882745
2023 SRSF1-mediated alternative splicing is required for spermatogenesis. International journal of biological sciences 17 37781512
2021 BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1. Genes 17 33670012
2021 A behavioral screen for mediators of age-dependent TDP-43 neurodegeneration identifies SF2/SRSF1 among a group of potent suppressors in both neurons and glia. PLoS genetics 17 34723963
2015 Genome-wide identification of SF1 and SF2 helicases from archaea. Gene 17 26456193

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