{"gene":"SRSF7","run_date":"2026-06-10T07:46:41","timeline":{"discoveries":[{"year":2020,"finding":"SRSF7 maintains protein homeostasis via a negative feedback mechanism: SRSF7 binding to its own pre-mRNA promotes inclusion of a poison cassette exon (PCE) and transcript degradation via NMD. At elevated SRSF7 levels, NMD is inhibited and two Split-ORF protein halves are translated from the bicistronic SRSF7-PCE transcript; the first half acts as a dominant-negative isoform that suppresses PCE inclusion and promotes retention of flanking introns containing repeated SRSF7 binding sites. Massive SRSF7 binding to these intronic sites and its oligomerization drives assembly of large nuclear bodies that sequester SRSF7 transcripts at their transcription site, preventing export and restoring normal protein levels.","method":"iCLIP, NMD reporter assays, overexpression/knockdown in murine P19 cells, live-cell imaging of nuclear body assembly, bicistronic reporter constructs, mutagenesis of binding sites","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (iCLIP, NMD assays, imaging, functional mutagenesis) in a single rigorous study establishing a complete autoregulatory circuit","pmids":["32123389"],"is_preprint":false},{"year":2021,"finding":"SRSF7 enhances proximal polyadenylation site (pPAS) usage in a concentration-dependent but splicing-independent manner by recruiting cleavage factor FIP1, generating short 3′UTRs. Protein domains unique to SRSF7 (absent from SRSF3) contribute to FIP1 recruitment. SRSF7 binds upstream of proximal PASs as determined by iCLIP.","method":"iCLIP, 3′-end sequencing, knockdown/overexpression, domain deletion/swap experiments, FIP1 co-immunoprecipitation","journal":"Genome biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — iCLIP combined with 3′-end sequencing, domain mutagenesis, and FIP1 interaction assays; multiple orthogonal methods in one study","pmids":["33706811"],"is_preprint":false},{"year":2018,"finding":"SRSF7 regulates alternative splicing of the apoptosis regulator Fas; knockdown of SRSF7 in colon and lung cancer cells inhibits proliferation and enhances apoptosis with Fas splicing changes as a defined molecular readout.","method":"siRNA knockdown, stable overexpression/knockdown cell lines, RT-PCR for Fas splice variants, MTS assay, flow cytometry","journal":"Oncology letters","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — loss-of-function with defined splicing phenotype replicated across two cell lines, but splicing mechanism not dissected further","pmids":["29556298"],"is_preprint":false},{"year":2021,"finding":"SRSF7 (together with SRSF1) binds to a clustered 55-nucleotide sequence motif (CAR-N) in the intronless lncRNA NKILA and interacts with TREX complex components UAP56 and ALYREF to promote NKILA nuclear export via the TREX/TAP pathway.","method":"In vitro RNP purification via CAR-N, mass spectrometry, siRNA screening, RNA immunoprecipitation, protein immunoprecipitation, NKILA CAR-N deletion knock-in models","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro RNP reconstitution, MS identification, reciprocal RNA/protein IP, and functional knock-in validation in a single comprehensive study","pmids":["34096602"],"is_preprint":false},{"year":2020,"finding":"Srsf7 mediates age-dependent alternative splicing (ADAS) in juvenile mice; Srsf7 suppression causes premature switching from juvenile to adult splice isoforms of anabolism-associated genes Eif4a2 and Rbm7, impairing anabolism and growth.","method":"RNA-seq of cerebral cortex/cardiomyocytes/hepatocytes at multiple postnatal timepoints, in vivo Srsf7 knockdown in mice, RT-PCR validation of specific splice events","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KD with defined splicing and physiological phenotype; single lab, single study","pmids":["32146325"],"is_preprint":false},{"year":2021,"finding":"SRSF7 facilitates Microprocessor cleavage of pri-miRNAs; SRSF7 functions with CRC and CNNC motifs in specific secondary structures and affects Microprocessor cleavage sites in human cells.","method":"High-throughput in vitro pri-miRNA cleavage assays, mutagenesis of RNA motifs/structures, cellular cleavage site mapping","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro reconstitution of Microprocessor cleavage with motif mutagenesis plus cellular validation; single lab","pmids":["36750366"],"is_preprint":false},{"year":2023,"finding":"SRSF7 downregulation induces cellular senescence by altering alternative splicing of MDM2, generating the MDM2-C variant which stabilizes p53; MDM2-C overexpression alone is sufficient to induce senescence in human diploid fibroblasts.","method":"RNA-seq of senescent cells, siRNA knockdown of SRSF7 in HDF, RT-PCR for MDM2 splice variants, Western blot for p53, MDM2-C overexpression, RS and OSIS senescence models","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — loss-of-function with defined AS variant and functional rescue; single lab, multiple senescence models","pmids":["38159247"],"is_preprint":false},{"year":2025,"finding":"CLK1 phosphorylates SRSF7 at serine 231 (S231) in a manner scaffolded by the circular RNA cALG8 (via its 34–85 nt and 109–160 nt regions); this phosphorylation promotes SRSF7-dependent alternative splicing of ATM to generate ATM203, enhancing ATM translational efficiency and DNA damage repair to confer gemcitabine resistance in PDAC.","method":"LC-MS identification of SRSF7 as cALG8-associated RBP, phospho-site mutagenesis, alternative splicing RT-PCR for ATM203, patient-derived organoids and xenografts, ASO rescue experiments","journal":"Drug resistance updates","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry identification plus functional mutagenesis (S231) and PDO/PDX validation; single lab","pmids":["40840404"],"is_preprint":false},{"year":2025,"finding":"SRSF7 modulates alternative splicing of pyruvate kinase (PKM) in lung fibroblasts, driving metabolic dysregulation (pro-fibrotic metabolic shift) and fibroblast activation; fibroblast-specific knockout of Srsf7 in mice confers resistance to bleomycin-induced pulmonary fibrosis.","method":"Conditional knockout mice, bleomycin model, RNA-seq for AS events, RT-PCR for PKM isoforms, metabolic assays, human IPF fibroblasts","journal":"Acta pharmaceutica Sinica. B","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined AS event and physiological phenotype; single lab","pmids":["40654335"],"is_preprint":false},{"year":2025,"finding":"SRSF7 depletion in iPSC-derived neurons reduces STMN2 (stathmin-2) abundance and impairs axonal regeneration; exogenous STMN2 rescues the axonal regeneration defect caused by SRSF7 depletion. Poly-PR (C9ORF72 DPR) selectively perturbs SRSF7 phosphorylation as shown by global phospho-proteomics.","method":"siRNA knockdown of SRSF7 in iPSC-derived neurons, global phospho-proteomics, axonal regeneration assays, STMN2 overexpression rescue","journal":"Acta neuropathologica communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular (STMN2) and cellular (axonal regeneration) phenotype plus rescue; single lab","pmids":["40140908"],"is_preprint":false},{"year":2023,"finding":"SRSF7 cooperates with the H4K20me1 histone methyltransferase KMT5a (SET8) at the Irf7 promoter to maximize STAT1 transcription factor binding and RNA Pol II elongation, driving transcription of IRF7 and optimal expression of interferon-stimulated genes in macrophages — a non-canonical transcriptional role for an SR protein.","method":"Genetic (KO/KD) and biochemical assays in macrophages, transcriptomic analysis, ChIP for STAT1 and Pol II, co-immunoprecipitation of SRSF7 with KMT5a","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic and biochemical assays with ChIP and Co-IP; preprint, single lab","pmids":["37503164"],"is_preprint":true},{"year":2025,"finding":"SRSF7 promotes HBV replication by binding to the epsilon stem-loop (ε) bulge and loop structures of HBV pgRNA and stabilizing pgRNA at the post-transcriptional level; deletion of ε bulge/loop significantly reduces SRSF7 binding capacity.","method":"Knockdown/overexpression in HBV replication cell models, RNA immunoprecipitation, ε element deletion mutants, Northern blot/RT-qPCR for HBV RNA levels","journal":"Journal of viral hepatitis","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus deletion mutagenesis of binding element; functional KD/OE; single lab","pmids":["40343745"],"is_preprint":false},{"year":2024,"finding":"Human SRSF7 (but not avian SRSF7) inhibits influenza A virus polymerase activity (PB2-627E variant); amino acids 206–228 of human SRSF7 (absent in avian SRSF7) are required for this inhibitory effect. PB2-627K-encoding influenza induces SRSF7 protein degradation via the lysosome pathway.","method":"siRNA knockdown, domain deletion mapping (aa 206–228), polymerase activity reporter assay, lysosome/proteasome inhibitor experiments","journal":"Microbes and infection","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion mapping with functional polymerase assay and pathway inhibitor experiments; single lab","pmids":["39134172"],"is_preprint":false},{"year":2024,"finding":"SRSF3 and SRSF7 antagonize SRSF1-mediated splicing-in of RIF1 cassette exon 32; DNA damage potentiates SRSF3/SRSF7 association with RIF1 pre-mRNA, increasing expression of the shorter RIF1-S isoform that lacks the phase-separating S/K cassette.","method":"RNA pulldown, CLIP, isoform-specific splicing reporters, DNA damage treatment, proteomic analysis of isoform-specific interactors","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint; SRSF7 role inferred from pulldown/CLIP data in context of a study focused primarily on RIF1, single lab","pmids":["bio_10.1101_2024.10.29.619708"],"is_preprint":true},{"year":2021,"finding":"SRSF7 specifically facilitates m6A methylation near its binding sites on mRNAs involved in cell proliferation/migration by recruiting the methyltransferase complex; two m6A sites on PBK mRNA are regulated by SRSF7 and recognized by IGF2BP2, partially mediating SRSF7 effects in GBM cells.","method":"m6A-seq, RIP, co-IP of SRSF7 with methyltransferase complex components, IGF2BP2 pulldown, knockdown/overexpression in GBM cells","journal":"Genomics, proteomics & bioinformatics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-IP and RIP without in vitro reconstitution; single lab; molecular mechanism of methyltransferase recruitment not dissected","pmids":["34954129"],"is_preprint":false},{"year":2025,"finding":"The PIWI-interacting RNA AB352916 (CRAPIR) binds to the RRM domain of Srsf7, inhibits Srsf7 ubiquitination/degradation, and thereby stabilizes Srsf7 to promote alternative splicing of Pkm, driving a pro-fibrotic glycolytic/mitochondrial metabolic shift in cardiac fibroblasts after myocardial infarction.","method":"RNA pulldown (RRM domain binding), ubiquitination assays, alternative splicing RT-PCR for Pkm isoforms, AAV-mediated myofibroblast-specific KD/OE in mice, metabolic assays, TGF-β1 fibrosis model","journal":"European journal of pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA pulldown with domain mapping, ubiquitination assay, in vivo AAV model with defined AS and metabolic phenotype; single lab","pmids":["42217722"],"is_preprint":false}],"current_model":"SRSF7 is an SR-family RNA-binding protein that maintains its own protein homeostasis through autoregulatory NMD and nuclear body assembly; it directly promotes proximal polyadenylation by recruiting FIP1, regulates alternative splicing of specific targets (Fas, MDM2, PKM, ATM, RIF1-Ex32) with downstream effects on apoptosis, senescence, metabolism, and DNA repair, stimulates Microprocessor cleavage of pri-miRNAs via CNNC/CRC motifs, facilitates nuclear export of intronless RNAs by bridging SRSF7-binding clusters to the TREX/TAP machinery, and additionally acts non-canonically at gene promoters (Irf7) by cooperating with the KMT5a methyltransferase to activate transcription in macrophages; its activity is regulated post-translationally by CLK1-mediated phosphorylation at S231 and by piRNA-dependent inhibition of its ubiquitination."},"narrative":{"mechanistic_narrative":"SRSF7 is an SR-family RNA-binding protein that governs RNA processing across splicing, 3′-end formation, miRNA biogenesis, and nuclear export, with downstream consequences for cell proliferation, senescence, metabolism, and DNA repair [PMID:32123389, PMID:33706811]. It maintains its own protein homeostasis through a negative-feedback circuit in which SRSF7 binding to its own pre-mRNA promotes inclusion of a poison cassette exon and NMD-coupled degradation; at elevated levels, intronic SRSF7 binding and oligomerization drive assembly of large nuclear bodies that sequester SRSF7 transcripts at their transcription site to restore normal protein levels [PMID:32123389]. In 3′-end processing, SRSF7 binds upstream of proximal polyadenylation sites and recruits the cleavage factor FIP1 to favor short 3′UTRs, a function dependent on domains unique to SRSF7 and independent of splicing [PMID:33706811]. As a splicing regulator it controls specific targets with defined cellular outputs: Fas splicing linked to proliferation and apoptosis [PMID:29556298], MDM2 splicing generating the MDM2-C variant that stabilizes p53 to drive senescence [PMID:38159247], PKM isoform choice that produces a pro-fibrotic metabolic shift in fibroblasts [PMID:40654335], and ATM splicing that enhances DNA damage repair [PMID:40840404]. SRSF7 also stimulates Microprocessor cleavage of pri-miRNAs through CNNC/CRC motifs [PMID:36750366] and, with SRSF1, bridges intronless RNAs such as NKILA to the TREX components UAP56 and ALYREF for nuclear export [PMID:34096602]. Its activity is regulated post-translationally by CLK1-mediated phosphorylation at serine 231 [PMID:40840404] and by piRNA binding to its RRM domain that blocks its ubiquitination and degradation [PMID:42217722].","teleology":[{"year":2018,"claim":"Establishing SRSF7 as a functionally relevant splicing regulator in cancer, the first finding tied its activity to a defined splicing target and cellular phenotype.","evidence":"siRNA knockdown and stable cell lines with RT-PCR for Fas splice variants, MTS and flow cytometry in colon and lung cancer cells","pmids":["29556298"],"confidence":"Medium","gaps":["Splicing mechanism on Fas not dissected at the RNA level","No direct binding map to the Fas pre-mRNA"]},{"year":2020,"claim":"Resolved how SRSF7 controls its own abundance, revealing an autoregulatory NMD-plus-nuclear-body circuit rather than simple feedback transcription.","evidence":"iCLIP, NMD reporter assays, live-cell imaging of nuclear body assembly and binding-site mutagenesis in murine P19 cells","pmids":["32123389"],"confidence":"High","gaps":["Structural basis of SRSF7 oligomerization unresolved","Whether the Split-ORF dominant-negative isoform exists at endogenous levels in other cell types unknown"]},{"year":2020,"claim":"Connected SRSF7 to developmental timing by showing it drives age-dependent splice-isoform switches controlling anabolism and growth.","evidence":"Postnatal RNA-seq across multiple tissues with in vivo knockdown and RT-PCR validation of Eif4a2 and Rbm7","pmids":["32146325"],"confidence":"Medium","gaps":["Direct binding of SRSF7 to the affected pre-mRNAs not shown","Mechanism timing the switch unknown"]},{"year":2021,"claim":"Defined a splicing-independent role in 3′-end formation, showing SRSF7 sets 3′UTR length by recruiting a polyadenylation factor.","evidence":"iCLIP, 3′-end sequencing, domain deletion/swap experiments and FIP1 co-immunoprecipitation","pmids":["33706811"],"confidence":"High","gaps":["Structural detail of the SRSF7–FIP1 interface not defined","Concentration dependence in vivo across tissues not mapped"]},{"year":2021,"claim":"Extended SRSF7 function to nuclear export of intronless RNAs by linking sequence-specific binding to the TREX/TAP machinery.","evidence":"In vitro RNP purification, mass spectrometry, reciprocal RNA/protein IP and CAR-N deletion knock-in for NKILA","pmids":["34096602"],"confidence":"High","gaps":["Generality across other intronless transcripts not established","Relative contributions of SRSF7 versus SRSF1 not separated"]},{"year":2021,"claim":"Implicated SRSF7 in miRNA biogenesis, showing it stimulates Microprocessor cleavage via defined RNA motifs.","evidence":"High-throughput in vitro pri-miRNA cleavage assays with motif/structure mutagenesis and cellular cleavage-site mapping","pmids":["36750366"],"confidence":"Medium","gaps":["Set of physiologically regulated miRNAs unknown","Whether SRSF7 directly contacts Microprocessor components not shown"]},{"year":2023,"claim":"Linked SRSF7 loss to senescence through an MDM2 splice variant that stabilizes p53, defining a tumor-suppressive splicing axis.","evidence":"RNA-seq of senescent cells, siRNA knockdown in fibroblasts, RT-PCR for MDM2 variants and MDM2-C overexpression rescue","pmids":["38159247"],"confidence":"Medium","gaps":["Direct SRSF7 binding on MDM2 pre-mRNA not mapped","Whether other p53-pathway splice events contribute unknown"]},{"year":2023,"claim":"Revealed a non-canonical chromatin role for SRSF7, acting at a promoter with a histone methyltransferase to activate transcription.","evidence":"Macrophage genetics, ChIP for STAT1 and Pol II, and co-immunoprecipitation of SRSF7 with KMT5a (preprint)","pmids":["37503164"],"confidence":"Medium","gaps":["Preprint not peer-reviewed","Whether the chromatin role generalizes beyond the Irf7 locus unknown"]},{"year":2024,"claim":"Identified SRSF7 as a host restriction factor for influenza polymerase, with a species-specific determinant region.","evidence":"siRNA knockdown, domain deletion mapping (aa 206–228), polymerase reporter assays and lysosome/proteasome inhibitor experiments","pmids":["39134172"],"confidence":"Medium","gaps":["Molecular mechanism of polymerase inhibition unresolved","How PB2-627K triggers lysosomal SRSF7 degradation not defined"]},{"year":2025,"claim":"Connected CLK1 phosphorylation of SRSF7 at S231 to ATM splicing and chemoresistance, providing a regulated-input-to-output axis.","evidence":"LC-MS of a circRNA-associated RBP, phospho-site mutagenesis, ATM203 RT-PCR and patient-derived organoid/xenograft validation in PDAC","pmids":["40840404"],"confidence":"Medium","gaps":["Whether S231 phosphorylation broadly tunes other SRSF7 targets unknown","Direct kinetics of CLK1–SRSF7 phosphorylation not measured"]},{"year":2025,"claim":"Established SRSF7 as a driver of pro-fibrotic metabolic reprogramming via PKM splicing in vivo.","evidence":"Fibroblast-specific conditional knockout mice, bleomycin model, RNA-seq, PKM RT-PCR and metabolic assays with human IPF fibroblasts","pmids":["40654335"],"confidence":"Medium","gaps":["Direct SRSF7 binding on PKM pre-mRNA not mapped here","Relationship to canonical PKM splicing regulators not resolved"]},{"year":2025,"claim":"Showed SRSF7 protein stability is controlled by a piRNA that binds its RRM and blocks ubiquitination, coupling SRSF7 levels to PKM splicing in cardiac fibrosis.","evidence":"RNA pulldown with RRM domain mapping, ubiquitination assays, AAV-mediated myofibroblast KD/OE in mice and metabolic assays","pmids":["42217722"],"confidence":"Medium","gaps":["Ubiquitin ligase acting on SRSF7 not identified","Whether piRNA control of SRSF7 operates outside cardiac fibroblasts unknown"]},{"year":2025,"claim":"Linked SRSF7 to neuronal axon regeneration via STMN2 abundance, with disease relevance to C9ORF72 dipeptide toxicity.","evidence":"siRNA knockdown in iPSC-derived neurons, global phospho-proteomics, axonal regeneration assays and STMN2 rescue","pmids":["40140908"],"confidence":"Medium","gaps":["Whether SRSF7 controls STMN2 through splicing or another mechanism not defined","Functional consequence of poly-PR-altered SRSF7 phosphorylation not established"]},{"year":null,"claim":"How SRSF7's diverse activities — autoregulation, 3′-end choice, splicing, export, miRNA processing, and chromatin action — are coordinately deployed across cell types and integrated with its phosphorylation and stability inputs remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking SRSF7 concentration, modification, and target selection","Genome-wide rules for proximal-PAS versus splicing versus export decisions undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,1,3,5,11]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[10]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,3,5]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[10]}],"complexes":[],"partners":["FIP1","UAP56","ALYREF","SRSF1","CLK1","KMT5A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q16629","full_name":"Serine/arginine-rich splicing factor 7","aliases":["Splicing factor 9G8","Splicing factor, arginine/serine-rich 7"],"length_aa":238,"mass_kda":27.4,"function":"Required for pre-mRNA splicing. Can also modulate alternative splicing in vitro. Represses the splicing of MAPT/Tau exon 10. May function as export adapter involved in mRNA nuclear export such as of histone H2A. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. RNA-binding is semi-sequence specific","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q16629/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SRSF7","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SRSF7","total_profiled":1310},"omim":[{"mim_id":"621181","title":"NF-KAPPA-B-INTERACTING LONG NONCODING RNA; NKILA","url":"https://www.omim.org/entry/621181"},{"mim_id":"605412","title":"RAB, MEMBER OF RAS ONCOGENE FAMILY-LIKE 2A; RABL2A","url":"https://www.omim.org/entry/605412"},{"mim_id":"600572","title":"SPLICING FACTOR, SERINE/ARGININE-RICH, 7; SRSF7","url":"https://www.omim.org/entry/600572"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SRSF7"},"hgnc":{"alias_symbol":["9G8","ZCRB2","HSSG1","AAG3","RBM37","ZCCHC20"],"prev_symbol":["SFRS7"]},"alphafold":{"accession":"Q16629","domains":[{"cath_id":"3.30.70.330","chopping":"11-80","consensus_level":"high","plddt":81.2276,"start":11,"end":80}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q16629","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q16629-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q16629-F1-predicted_aligned_error_v6.png","plddt_mean":57.91},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SRSF7","jax_strain_url":"https://www.jax.org/strain/search?query=SRSF7"},"sequence":{"accession":"Q16629","fasta_url":"https://rest.uniprot.org/uniprotkb/Q16629.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q16629/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q16629"}},"corpus_meta":[{"pmid":"32123389","id":"PMC_32123389","title":"SRSF7 maintains its homeostasis through the expression of Split-ORFs and nuclear body assembly.","date":"2020","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/32123389","citation_count":62,"is_preprint":false},{"pmid":"33706811","id":"PMC_33706811","title":"SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels.","date":"2021","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/33706811","citation_count":53,"is_preprint":false},{"pmid":"29556298","id":"PMC_29556298","title":"SRSF7 knockdown promotes apoptosis of colon and lung cancer cells.","date":"2018","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/29556298","citation_count":51,"is_preprint":false},{"pmid":"32141554","id":"PMC_32141554","title":"Long non-coding RNA MALAT1 regulates proliferation, apoptosis, migration and invasion via miR-374b-5p/SRSF7 axis in non-small cell lung cancer.","date":"2020","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32141554","citation_count":48,"is_preprint":false},{"pmid":"27664584","id":"PMC_27664584","title":"microRNAs target SRSF7 splicing factor to modulate the expression of osteopontin splice variants in renal cancer cells.","date":"2016","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/27664584","citation_count":39,"is_preprint":false},{"pmid":"34954129","id":"PMC_34954129","title":"Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.","date":"2021","source":"Genomics, proteomics & bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/34954129","citation_count":32,"is_preprint":false},{"pmid":"34096602","id":"PMC_34096602","title":"Sequence-dependent recruitment of SRSF1 and SRSF7 to intronless lncRNA NKILA promotes nuclear export via the TREX/TAP pathway.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/34096602","citation_count":24,"is_preprint":false},{"pmid":"32146325","id":"PMC_32146325","title":"Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice.","date":"2020","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/32146325","citation_count":22,"is_preprint":false},{"pmid":"31555692","id":"PMC_31555692","title":"MicroRNA-188 aggravates contrast-induced apoptosis by targeting SRSF7 in novel isotonic contrast-induced acute kidney injury rat models and renal tubular epithelial cells.","date":"2019","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31555692","citation_count":19,"is_preprint":false},{"pmid":"35037349","id":"PMC_35037349","title":"Circ_0006006 facilitates non-small cell lung cancer progression by modulating miR-924/SRSF7 axis.","date":"2022","source":"The journal of gene 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At elevated SRSF7 levels, NMD is inhibited and two Split-ORF protein halves are translated from the bicistronic SRSF7-PCE transcript; the first half acts as a dominant-negative isoform that suppresses PCE inclusion and promotes retention of flanking introns containing repeated SRSF7 binding sites. Massive SRSF7 binding to these intronic sites and its oligomerization drives assembly of large nuclear bodies that sequester SRSF7 transcripts at their transcription site, preventing export and restoring normal protein levels.\",\n      \"method\": \"iCLIP, NMD reporter assays, overexpression/knockdown in murine P19 cells, live-cell imaging of nuclear body assembly, bicistronic reporter constructs, mutagenesis of binding sites\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (iCLIP, NMD assays, imaging, functional mutagenesis) in a single rigorous study establishing a complete autoregulatory circuit\",\n      \"pmids\": [\"32123389\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SRSF7 enhances proximal polyadenylation site (pPAS) usage in a concentration-dependent but splicing-independent manner by recruiting cleavage factor FIP1, generating short 3′UTRs. Protein domains unique to SRSF7 (absent from SRSF3) contribute to FIP1 recruitment. SRSF7 binds upstream of proximal PASs as determined by iCLIP.\",\n      \"method\": \"iCLIP, 3′-end sequencing, knockdown/overexpression, domain deletion/swap experiments, FIP1 co-immunoprecipitation\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — iCLIP combined with 3′-end sequencing, domain mutagenesis, and FIP1 interaction assays; multiple orthogonal methods in one study\",\n      \"pmids\": [\"33706811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SRSF7 regulates alternative splicing of the apoptosis regulator Fas; knockdown of SRSF7 in colon and lung cancer cells inhibits proliferation and enhances apoptosis with Fas splicing changes as a defined molecular readout.\",\n      \"method\": \"siRNA knockdown, stable overexpression/knockdown cell lines, RT-PCR for Fas splice variants, MTS assay, flow cytometry\",\n      \"journal\": \"Oncology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — loss-of-function with defined splicing phenotype replicated across two cell lines, but splicing mechanism not dissected further\",\n      \"pmids\": [\"29556298\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SRSF7 (together with SRSF1) binds to a clustered 55-nucleotide sequence motif (CAR-N) in the intronless lncRNA NKILA and interacts with TREX complex components UAP56 and ALYREF to promote NKILA nuclear export via the TREX/TAP pathway.\",\n      \"method\": \"In vitro RNP purification via CAR-N, mass spectrometry, siRNA screening, RNA immunoprecipitation, protein immunoprecipitation, NKILA CAR-N deletion knock-in models\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro RNP reconstitution, MS identification, reciprocal RNA/protein IP, and functional knock-in validation in a single comprehensive study\",\n      \"pmids\": [\"34096602\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Srsf7 mediates age-dependent alternative splicing (ADAS) in juvenile mice; Srsf7 suppression causes premature switching from juvenile to adult splice isoforms of anabolism-associated genes Eif4a2 and Rbm7, impairing anabolism and growth.\",\n      \"method\": \"RNA-seq of cerebral cortex/cardiomyocytes/hepatocytes at multiple postnatal timepoints, in vivo Srsf7 knockdown in mice, RT-PCR validation of specific splice events\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KD with defined splicing and physiological phenotype; single lab, single study\",\n      \"pmids\": [\"32146325\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SRSF7 facilitates Microprocessor cleavage of pri-miRNAs; SRSF7 functions with CRC and CNNC motifs in specific secondary structures and affects Microprocessor cleavage sites in human cells.\",\n      \"method\": \"High-throughput in vitro pri-miRNA cleavage assays, mutagenesis of RNA motifs/structures, cellular cleavage site mapping\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro reconstitution of Microprocessor cleavage with motif mutagenesis plus cellular validation; single lab\",\n      \"pmids\": [\"36750366\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SRSF7 downregulation induces cellular senescence by altering alternative splicing of MDM2, generating the MDM2-C variant which stabilizes p53; MDM2-C overexpression alone is sufficient to induce senescence in human diploid fibroblasts.\",\n      \"method\": \"RNA-seq of senescent cells, siRNA knockdown of SRSF7 in HDF, RT-PCR for MDM2 splice variants, Western blot for p53, MDM2-C overexpression, RS and OSIS senescence models\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — loss-of-function with defined AS variant and functional rescue; single lab, multiple senescence models\",\n      \"pmids\": [\"38159247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CLK1 phosphorylates SRSF7 at serine 231 (S231) in a manner scaffolded by the circular RNA cALG8 (via its 34–85 nt and 109–160 nt regions); this phosphorylation promotes SRSF7-dependent alternative splicing of ATM to generate ATM203, enhancing ATM translational efficiency and DNA damage repair to confer gemcitabine resistance in PDAC.\",\n      \"method\": \"LC-MS identification of SRSF7 as cALG8-associated RBP, phospho-site mutagenesis, alternative splicing RT-PCR for ATM203, patient-derived organoids and xenografts, ASO rescue experiments\",\n      \"journal\": \"Drug resistance updates\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry identification plus functional mutagenesis (S231) and PDO/PDX validation; single lab\",\n      \"pmids\": [\"40840404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SRSF7 modulates alternative splicing of pyruvate kinase (PKM) in lung fibroblasts, driving metabolic dysregulation (pro-fibrotic metabolic shift) and fibroblast activation; fibroblast-specific knockout of Srsf7 in mice confers resistance to bleomycin-induced pulmonary fibrosis.\",\n      \"method\": \"Conditional knockout mice, bleomycin model, RNA-seq for AS events, RT-PCR for PKM isoforms, metabolic assays, human IPF fibroblasts\",\n      \"journal\": \"Acta pharmaceutica Sinica. B\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined AS event and physiological phenotype; single lab\",\n      \"pmids\": [\"40654335\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SRSF7 depletion in iPSC-derived neurons reduces STMN2 (stathmin-2) abundance and impairs axonal regeneration; exogenous STMN2 rescues the axonal regeneration defect caused by SRSF7 depletion. Poly-PR (C9ORF72 DPR) selectively perturbs SRSF7 phosphorylation as shown by global phospho-proteomics.\",\n      \"method\": \"siRNA knockdown of SRSF7 in iPSC-derived neurons, global phospho-proteomics, axonal regeneration assays, STMN2 overexpression rescue\",\n      \"journal\": \"Acta neuropathologica communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular (STMN2) and cellular (axonal regeneration) phenotype plus rescue; single lab\",\n      \"pmids\": [\"40140908\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SRSF7 cooperates with the H4K20me1 histone methyltransferase KMT5a (SET8) at the Irf7 promoter to maximize STAT1 transcription factor binding and RNA Pol II elongation, driving transcription of IRF7 and optimal expression of interferon-stimulated genes in macrophages — a non-canonical transcriptional role for an SR protein.\",\n      \"method\": \"Genetic (KO/KD) and biochemical assays in macrophages, transcriptomic analysis, ChIP for STAT1 and Pol II, co-immunoprecipitation of SRSF7 with KMT5a\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic and biochemical assays with ChIP and Co-IP; preprint, single lab\",\n      \"pmids\": [\"37503164\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SRSF7 promotes HBV replication by binding to the epsilon stem-loop (ε) bulge and loop structures of HBV pgRNA and stabilizing pgRNA at the post-transcriptional level; deletion of ε bulge/loop significantly reduces SRSF7 binding capacity.\",\n      \"method\": \"Knockdown/overexpression in HBV replication cell models, RNA immunoprecipitation, ε element deletion mutants, Northern blot/RT-qPCR for HBV RNA levels\",\n      \"journal\": \"Journal of viral hepatitis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus deletion mutagenesis of binding element; functional KD/OE; single lab\",\n      \"pmids\": [\"40343745\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Human SRSF7 (but not avian SRSF7) inhibits influenza A virus polymerase activity (PB2-627E variant); amino acids 206–228 of human SRSF7 (absent in avian SRSF7) are required for this inhibitory effect. PB2-627K-encoding influenza induces SRSF7 protein degradation via the lysosome pathway.\",\n      \"method\": \"siRNA knockdown, domain deletion mapping (aa 206–228), polymerase activity reporter assay, lysosome/proteasome inhibitor experiments\",\n      \"journal\": \"Microbes and infection\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion mapping with functional polymerase assay and pathway inhibitor experiments; single lab\",\n      \"pmids\": [\"39134172\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SRSF3 and SRSF7 antagonize SRSF1-mediated splicing-in of RIF1 cassette exon 32; DNA damage potentiates SRSF3/SRSF7 association with RIF1 pre-mRNA, increasing expression of the shorter RIF1-S isoform that lacks the phase-separating S/K cassette.\",\n      \"method\": \"RNA pulldown, CLIP, isoform-specific splicing reporters, DNA damage treatment, proteomic analysis of isoform-specific interactors\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint; SRSF7 role inferred from pulldown/CLIP data in context of a study focused primarily on RIF1, single lab\",\n      \"pmids\": [\"bio_10.1101_2024.10.29.619708\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SRSF7 specifically facilitates m6A methylation near its binding sites on mRNAs involved in cell proliferation/migration by recruiting the methyltransferase complex; two m6A sites on PBK mRNA are regulated by SRSF7 and recognized by IGF2BP2, partially mediating SRSF7 effects in GBM cells.\",\n      \"method\": \"m6A-seq, RIP, co-IP of SRSF7 with methyltransferase complex components, IGF2BP2 pulldown, knockdown/overexpression in GBM cells\",\n      \"journal\": \"Genomics, proteomics & bioinformatics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-IP and RIP without in vitro reconstitution; single lab; molecular mechanism of methyltransferase recruitment not dissected\",\n      \"pmids\": [\"34954129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The PIWI-interacting RNA AB352916 (CRAPIR) binds to the RRM domain of Srsf7, inhibits Srsf7 ubiquitination/degradation, and thereby stabilizes Srsf7 to promote alternative splicing of Pkm, driving a pro-fibrotic glycolytic/mitochondrial metabolic shift in cardiac fibroblasts after myocardial infarction.\",\n      \"method\": \"RNA pulldown (RRM domain binding), ubiquitination assays, alternative splicing RT-PCR for Pkm isoforms, AAV-mediated myofibroblast-specific KD/OE in mice, metabolic assays, TGF-β1 fibrosis model\",\n      \"journal\": \"European journal of pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA pulldown with domain mapping, ubiquitination assay, in vivo AAV model with defined AS and metabolic phenotype; single lab\",\n      \"pmids\": [\"42217722\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SRSF7 is an SR-family RNA-binding protein that maintains its own protein homeostasis through autoregulatory NMD and nuclear body assembly; it directly promotes proximal polyadenylation by recruiting FIP1, regulates alternative splicing of specific targets (Fas, MDM2, PKM, ATM, RIF1-Ex32) with downstream effects on apoptosis, senescence, metabolism, and DNA repair, stimulates Microprocessor cleavage of pri-miRNAs via CNNC/CRC motifs, facilitates nuclear export of intronless RNAs by bridging SRSF7-binding clusters to the TREX/TAP machinery, and additionally acts non-canonically at gene promoters (Irf7) by cooperating with the KMT5a methyltransferase to activate transcription in macrophages; its activity is regulated post-translationally by CLK1-mediated phosphorylation at S231 and by piRNA-dependent inhibition of its ubiquitination.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRSF7 is an SR-family RNA-binding protein that governs RNA processing across splicing, 3′-end formation, miRNA biogenesis, and nuclear export, with downstream consequences for cell proliferation, senescence, metabolism, and DNA repair [#0, #1]. It maintains its own protein homeostasis through a negative-feedback circuit in which SRSF7 binding to its own pre-mRNA promotes inclusion of a poison cassette exon and NMD-coupled degradation; at elevated levels, intronic SRSF7 binding and oligomerization drive assembly of large nuclear bodies that sequester SRSF7 transcripts at their transcription site to restore normal protein levels [#0]. In 3′-end processing, SRSF7 binds upstream of proximal polyadenylation sites and recruits the cleavage factor FIP1 to favor short 3′UTRs, a function dependent on domains unique to SRSF7 and independent of splicing [#1]. As a splicing regulator it controls specific targets with defined cellular outputs: Fas splicing linked to proliferation and apoptosis [#2], MDM2 splicing generating the MDM2-C variant that stabilizes p53 to drive senescence [#6], PKM isoform choice that produces a pro-fibrotic metabolic shift in fibroblasts [#8], and ATM splicing that enhances DNA damage repair [#7]. SRSF7 also stimulates Microprocessor cleavage of pri-miRNAs through CNNC/CRC motifs [#5] and, with SRSF1, bridges intronless RNAs such as NKILA to the TREX components UAP56 and ALYREF for nuclear export [#3]. Its activity is regulated post-translationally by CLK1-mediated phosphorylation at serine 231 [#7] and by piRNA binding to its RRM domain that blocks its ubiquitination and degradation [#15].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing SRSF7 as a functionally relevant splicing regulator in cancer, the first finding tied its activity to a defined splicing target and cellular phenotype.\",\n      \"evidence\": \"siRNA knockdown and stable cell lines with RT-PCR for Fas splice variants, MTS and flow cytometry in colon and lung cancer cells\",\n      \"pmids\": [\"29556298\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Splicing mechanism on Fas not dissected at the RNA level\", \"No direct binding map to the Fas pre-mRNA\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved how SRSF7 controls its own abundance, revealing an autoregulatory NMD-plus-nuclear-body circuit rather than simple feedback transcription.\",\n      \"evidence\": \"iCLIP, NMD reporter assays, live-cell imaging of nuclear body assembly and binding-site mutagenesis in murine P19 cells\",\n      \"pmids\": [\"32123389\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of SRSF7 oligomerization unresolved\", \"Whether the Split-ORF dominant-negative isoform exists at endogenous levels in other cell types unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected SRSF7 to developmental timing by showing it drives age-dependent splice-isoform switches controlling anabolism and growth.\",\n      \"evidence\": \"Postnatal RNA-seq across multiple tissues with in vivo knockdown and RT-PCR validation of Eif4a2 and Rbm7\",\n      \"pmids\": [\"32146325\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of SRSF7 to the affected pre-mRNAs not shown\", \"Mechanism timing the switch unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined a splicing-independent role in 3′-end formation, showing SRSF7 sets 3′UTR length by recruiting a polyadenylation factor.\",\n      \"evidence\": \"iCLIP, 3′-end sequencing, domain deletion/swap experiments and FIP1 co-immunoprecipitation\",\n      \"pmids\": [\"33706811\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural detail of the SRSF7–FIP1 interface not defined\", \"Concentration dependence in vivo across tissues not mapped\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended SRSF7 function to nuclear export of intronless RNAs by linking sequence-specific binding to the TREX/TAP machinery.\",\n      \"evidence\": \"In vitro RNP purification, mass spectrometry, reciprocal RNA/protein IP and CAR-N deletion knock-in for NKILA\",\n      \"pmids\": [\"34096602\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality across other intronless transcripts not established\", \"Relative contributions of SRSF7 versus SRSF1 not separated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Implicated SRSF7 in miRNA biogenesis, showing it stimulates Microprocessor cleavage via defined RNA motifs.\",\n      \"evidence\": \"High-throughput in vitro pri-miRNA cleavage assays with motif/structure mutagenesis and cellular cleavage-site mapping\",\n      \"pmids\": [\"36750366\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Set of physiologically regulated miRNAs unknown\", \"Whether SRSF7 directly contacts Microprocessor components not shown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linked SRSF7 loss to senescence through an MDM2 splice variant that stabilizes p53, defining a tumor-suppressive splicing axis.\",\n      \"evidence\": \"RNA-seq of senescent cells, siRNA knockdown in fibroblasts, RT-PCR for MDM2 variants and MDM2-C overexpression rescue\",\n      \"pmids\": [\"38159247\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SRSF7 binding on MDM2 pre-mRNA not mapped\", \"Whether other p53-pathway splice events contribute unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed a non-canonical chromatin role for SRSF7, acting at a promoter with a histone methyltransferase to activate transcription.\",\n      \"evidence\": \"Macrophage genetics, ChIP for STAT1 and Pol II, and co-immunoprecipitation of SRSF7 with KMT5a (preprint)\",\n      \"pmids\": [\"37503164\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint not peer-reviewed\", \"Whether the chromatin role generalizes beyond the Irf7 locus unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified SRSF7 as a host restriction factor for influenza polymerase, with a species-specific determinant region.\",\n      \"evidence\": \"siRNA knockdown, domain deletion mapping (aa 206–228), polymerase reporter assays and lysosome/proteasome inhibitor experiments\",\n      \"pmids\": [\"39134172\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of polymerase inhibition unresolved\", \"How PB2-627K triggers lysosomal SRSF7 degradation not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected CLK1 phosphorylation of SRSF7 at S231 to ATM splicing and chemoresistance, providing a regulated-input-to-output axis.\",\n      \"evidence\": \"LC-MS of a circRNA-associated RBP, phospho-site mutagenesis, ATM203 RT-PCR and patient-derived organoid/xenograft validation in PDAC\",\n      \"pmids\": [\"40840404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether S231 phosphorylation broadly tunes other SRSF7 targets unknown\", \"Direct kinetics of CLK1–SRSF7 phosphorylation not measured\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established SRSF7 as a driver of pro-fibrotic metabolic reprogramming via PKM splicing in vivo.\",\n      \"evidence\": \"Fibroblast-specific conditional knockout mice, bleomycin model, RNA-seq, PKM RT-PCR and metabolic assays with human IPF fibroblasts\",\n      \"pmids\": [\"40654335\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SRSF7 binding on PKM pre-mRNA not mapped here\", \"Relationship to canonical PKM splicing regulators not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed SRSF7 protein stability is controlled by a piRNA that binds its RRM and blocks ubiquitination, coupling SRSF7 levels to PKM splicing in cardiac fibrosis.\",\n      \"evidence\": \"RNA pulldown with RRM domain mapping, ubiquitination assays, AAV-mediated myofibroblast KD/OE in mice and metabolic assays\",\n      \"pmids\": [\"42217722\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitin ligase acting on SRSF7 not identified\", \"Whether piRNA control of SRSF7 operates outside cardiac fibroblasts unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked SRSF7 to neuronal axon regeneration via STMN2 abundance, with disease relevance to C9ORF72 dipeptide toxicity.\",\n      \"evidence\": \"siRNA knockdown in iPSC-derived neurons, global phospho-proteomics, axonal regeneration assays and STMN2 rescue\",\n      \"pmids\": [\"40140908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SRSF7 controls STMN2 through splicing or another mechanism not defined\", \"Functional consequence of poly-PR-altered SRSF7 phosphorylation not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SRSF7's diverse activities — autoregulation, 3′-end choice, splicing, export, miRNA processing, and chromatin action — are coordinately deployed across cell types and integrated with its phosphorylation and stability inputs remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking SRSF7 concentration, modification, and target selection\", \"Genome-wide rules for proximal-PAS versus splicing versus export decisions undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1, 3, 5, 11]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016604\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 3, 5]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"FIP1\", \"UAP56\", \"ALYREF\", \"SRSF1\", \"CLK1\", \"KMT5a\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":6,"faith_total":6,"faith_pct":100.0}}