{"gene":"SNRPF","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2003,"finding":"The Sm-F protein (SNRPF) is proteolytically cleaved by caspases during apoptosis, generating a 9-kDa apoptotic fragment. The cleavage site was mapped near the C-terminus at EEED(81)↓G. The 9-kDa fragment remains associated with U snRNP complexes in apoptotic cells. Caspase-8 and other caspases are implicated in this cleavage. A C-terminally truncated mutant representing the modified form can form an Sm E-F-G complex in vitro that is recognized by anti-Sm patient sera.","method":"Caspase inhibitor assays, site-directed mutagenesis, in vitro Sm complex reconstitution, immunoprecipitation with patient anti-Sm sera","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 1 / Strong — cleavage site mapped by mutagenesis, in vitro reconstitution of truncated Sm E-F-G complex, multiple orthogonal methods in a single rigorous study","pmids":["12728255"],"is_preprint":false},{"year":2002,"finding":"SNRPF (Sm-F) undergoes caspase-mediated cleavage during apoptosis and the U1 snRNP complex (including Sm-F) translocates from its normal nuclear localization to apoptotic bodies near the cell surface during apoptosis. This redistribution may expose modified snRNP components to the immune system.","method":"Subcellular fractionation and localization studies of apoptotic cells, biochemical analysis of U1 snRNP complex modifications during apoptosis","journal":"The Israel Medical Association journal : IMAJ","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence described, but abstract is a review/summary and does not detail all primary methods; single lab","pmids":["12440236"],"is_preprint":false},{"year":2017,"finding":"Knockdown of UCH-L5 (a deubiquitinase) increases both mRNA and protein levels of SNRPF. UCH-L5 overexpression inhibits glioma cell migration and invasion, and SNRPF-siRNA independently inhibits migration and invasion of U87MG glioma cells, placing SNRPF downstream of UCH-L5 in a pathway regulating glioma cell motility.","method":"siRNA knockdown of SNRPF, UCH-L5 knockdown/overexpression, cell migration and invasion assays, mRNA and protein quantification in U87MG/U251 and 293T cells","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via siRNA with defined cellular phenotype (migration/invasion), two cell lines, but single lab and no biochemical mechanism of UCH-L5 acting on SNRPF protein directly","pmids":["29371935"],"is_preprint":false},{"year":2025,"finding":"Mycobacterium tuberculosis secreted protein Rv1435c/hsr1 facilitates direct interaction between Mtb phagosomes and SNRPF (a key spliceosomal snRNP component), disrupting host snRNP biogenesis and causing specific exon-skipping events in host mRNA. Genetic deletion of hsr1 reverses these exon-skipping events, and hsr1-dependent SNRPF staining is observed in infected mouse tissues and human intestinal tuberculosis biopsies.","method":"Yeast-2-hybrid screen, in-cell interaction assays, bacterial genetic deletion (Δhsr1), RNA splicing analysis, immunostaining of infected mouse and human tissues","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (Y2H, in-cell assays, genetic deletion with phenotypic rescue, in vivo validation), published in high-impact journal","pmids":["40601628"],"is_preprint":false},{"year":2026,"finding":"SNRPF, a core spliceosomal component, promotes ovarian cancer progression through a feedback loop. SNRPF depletion induces intron 6 retention in DDX24 pre-mRNA, disrupting the Helicase_C domain and generating premature termination codons that activate nonsense-mediated decay (NMD), reducing DDX24 protein. DDX24 depletion similarly promotes intron 2 retention in E2F4, causing NMD-mediated E2F4 downregulation. E2F4 directly binds the SNRPF promoter, forming a self-sustaining SNRPF-DDX24-E2F4 axis. Antisense oligonucleotide-mediated inhibition of SNRPF disrupts this loop and impairs tumor growth in vitro, in vivo, and in patient-derived xenografts.","method":"Transcriptomic and proteomic analyses, siRNA knockdown, intron retention analysis, NMD assays, ChIP/promoter binding assays, antisense oligonucleotide treatment, xenograft tumor models including patient-derived xenografts","journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (splicing analysis, NMD validation, promoter binding, in vivo xenograft and PDX), mechanistically defined feedback loop with rescue experiments","pmids":["42107058"],"is_preprint":false},{"year":2026,"finding":"SNRPF binds to the pre-mRNA of TMED2 (transmembrane P24 trafficking protein 2), preventing intron 2 retention and subsequent nonsense-mediated decay, thereby maintaining TMED2 protein abundance. TMED2 in turn directly interacts with cGAS, promoting cGAS activation and downstream STING/TBK1/IRF3 signaling, leading to IFN-β, ISG15, and cytokine production. This SNRPF/TMED2/cGAS-STING axis promotes hepatocellular carcinoma growth and progression.","method":"RNA immunoprecipitation, reporter gene assays, co-immunoprecipitation, GST pull-down assays, overexpression/knockdown functional assays, cGAS/STING inhibitor rescue experiments, orthotopic xenograft mouse model","journal":"International journal of biological macromolecules","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — RNA immunoprecipitation and GST pull-down establish direct binding, multiple orthogonal methods (RIP, Co-IP, GST pulldown, inhibitor rescue, in vivo orthotopic model), single lab but rigorous","pmids":["41786173"],"is_preprint":false}],"current_model":"SNRPF (Sm-F) is a core spliceosomal Sm protein that functions within U snRNP complexes to regulate pre-mRNA splicing; it is proteolytically cleaved by caspases (at EEED81↓G) during apoptosis generating a 9-kDa fragment that remains snRNP-associated and relocates to apoptotic bodies, its abundance is regulated downstream of the deubiquitinase UCH-L5 to control glioma cell invasion, it is directly targeted by the M. tuberculosis virulence factor Rv1435c/hsr1 to disrupt host snRNP biogenesis and alter exon usage, it binds TMED2 pre-mRNA to prevent intron retention and NMD thereby activating a TMED2/cGAS-STING oncogenic axis in hepatocellular carcinoma, and it forms a self-sustaining splicing-transcription feedback loop (SNRPF-DDX24-E2F4) in ovarian cancer whereby it prevents intron retention/NMD of DDX24 and E2F4 while E2F4 transcriptionally drives SNRPF expression."},"narrative":{"mechanistic_narrative":"SNRPF (Sm-F) is a core spliceosomal Sm protein that assembles into U snRNP complexes and governs pre-mRNA splicing fidelity, with emerging roles in apoptosis, host-pathogen interaction, and oncogenesis [PMID:12728255, PMID:40601628, PMID:42107058]. During apoptosis, SNRPF is proteolytically cleaved by caspases at EEED81↓G to yield a 9-kDa fragment that remains associated with U snRNP complexes; concomitantly the U1 snRNP relocates from the nucleus to apoptotic bodies near the cell surface, exposing modified snRNP components recognized by anti-Sm patient sera [PMID:12728255, PMID:12440236]. By controlling splice-site selection, SNRPF prevents pathological intron retention in specific transcripts: it binds DDX24 and E2F4 pre-mRNAs to avert intron retention and nonsense-mediated decay, sustaining a self-reinforcing SNRPF-DDX24-E2F4 feedback loop in ovarian cancer, and it binds TMED2 pre-mRNA to maintain TMED2 protein and drive a TMED2/cGAS-STING signaling axis in hepatocellular carcinoma [PMID:42107058, PMID:41786173]. SNRPF acts downstream of the deubiquitinase UCH-L5 to promote glioma cell migration and invasion [PMID:29371935], and it is directly engaged by the M. tuberculosis virulence factor Rv1435c/hsr1, which disrupts host snRNP biogenesis and induces specific exon-skipping events during infection [PMID:40601628]. Antisense oligonucleotide targeting of SNRPF impairs tumor growth in vitro and in xenograft models, establishing it as a tractable splicing-dependent oncogenic dependency [PMID:42107058].","teleology":[{"year":2002,"claim":"Established that SNRPF-containing snRNPs are not static during cell death but undergo regulated subcellular redistribution, linking spliceosome components to autoimmune antigen exposure.","evidence":"Subcellular fractionation and localization analysis of U1 snRNP in apoptotic cells","pmids":["12440236"],"confidence":"Medium","gaps":["Review-style summary without full primary methods","Mechanism of translocation to apoptotic bodies not defined","Single lab"]},{"year":2003,"claim":"Defined the molecular event behind SNRPF apoptotic modification by mapping a precise caspase cleavage site and showing the cleaved fragment retains snRNP association and antigenicity.","evidence":"Caspase inhibitor assays, site-directed mutagenesis of EEED81↓G, in vitro Sm E-F-G reconstitution, IP with anti-Sm patient sera","pmids":["12728255"],"confidence":"High","gaps":["Functional consequence of cleavage for splicing not determined","Which specific caspase is primary in vivo not resolved","Link to autoimmune disease causation not established"]},{"year":2017,"claim":"Placed SNRPF in a cancer cell-motility pathway downstream of a deubiquitinase, the first link of SNRPF abundance to a malignant phenotype.","evidence":"siRNA knockdown of SNRPF and UCH-L5, migration/invasion assays in U87MG/U251 glioma cells","pmids":["29371935"],"confidence":"Medium","gaps":["No direct biochemical mechanism linking UCH-L5 to SNRPF protein","Splicing targets mediating invasion not identified","Single lab"]},{"year":2025,"claim":"Revealed SNRPF as a direct host target of a bacterial virulence factor, showing pathogens can co-opt the spliceosome to remodel host mRNA processing.","evidence":"Yeast-2-hybrid, in-cell interaction assays, Δhsr1 genetic deletion with splicing rescue, immunostaining of infected mouse and human biopsies","pmids":["40601628"],"confidence":"High","gaps":["Functional outcome of exon-skipping for infection survival not fully resolved","Structural basis of hsr1-SNRPF interaction unknown"]},{"year":2026,"claim":"Demonstrated that SNRPF promotes tumorigenesis through transcript-specific intron-retention control, defining concrete downstream effector axes in two cancer types.","evidence":"RNA-IP, intron retention/NMD assays, ChIP promoter binding, Co-IP/GST pull-down, antisense oligonucleotide treatment, orthotopic and patient-derived xenografts","pmids":["42107058","41786173"],"confidence":"High","gaps":["Whether SNRPF selectivity for these transcripts is sequence-specific or context-driven not resolved","Generality of the feedback loops beyond ovarian and hepatocellular carcinoma untested"]},{"year":null,"claim":"How SNRPF achieves transcript-selective control of intron retention versus its general role in core spliceosome assembly remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model for SNRPF-pre-mRNA selectivity","Determinants of which introns escape retention upon SNRPF loss undefined","Relationship between caspase cleavage and oncogenic splicing roles unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[4,5]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,4,5]}],"complexes":["U snRNP","U1 snRNP","Sm E-F-G complex"],"partners":["TMED2","DDX24","E2F4","RV1435C/HSR1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P62306","full_name":"Small nuclear ribonucleoprotein F","aliases":["Sm protein F","Sm-F","SmF"],"length_aa":86,"mass_kda":9.7,"function":"Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:28781166). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319)","subcellular_location":"Cytoplasm, cytosol; Nucleus","url":"https://www.uniprot.org/uniprotkb/P62306/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SNRPF","classification":"Common Essential","n_dependent_lines":1208,"n_total_lines":1208,"dependency_fraction":1.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000139343","cell_line_id":"CID001461","localizations":[{"compartment":"chromatin","grade":3}],"interactors":[{"gene":"CLNS1A","stoichiometry":10.0},{"gene":"FUS","stoichiometry":10.0},{"gene":"PRPF8","stoichiometry":10.0},{"gene":"SF3B1","stoichiometry":10.0},{"gene":"SF3B2","stoichiometry":10.0},{"gene":"SF3B6","stoichiometry":10.0},{"gene":"SNRPA","stoichiometry":10.0},{"gene":"SNRPB","stoichiometry":10.0},{"gene":"SNRPC","stoichiometry":10.0},{"gene":"SNRPD2","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001461","total_profiled":1310},"omim":[{"mim_id":"603542","title":"SMALL NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE G; SNRPG","url":"https://www.omim.org/entry/603542"},{"mim_id":"603541","title":"SMALL NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE F; SNRPF","url":"https://www.omim.org/entry/603541"},{"mim_id":"180740","title":"SMALL NUCLEAR RIBONUCLEOPROTEIN, U1 SUBUNIT, 70-KD; SNRNP70","url":"https://www.omim.org/entry/180740"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNRPF"},"hgnc":{"alias_symbol":["Sm-F"],"prev_symbol":[]},"alphafold":{"accession":"P62306","domains":[{"cath_id":"2.30.30.100","chopping":"15-73","consensus_level":"high","plddt":97.1407,"start":15,"end":73}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P62306","model_url":"https://alphafold.ebi.ac.uk/files/AF-P62306-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P62306-F1-predicted_aligned_error_v6.png","plddt_mean":90.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNRPF","jax_strain_url":"https://www.jax.org/strain/search?query=SNRPF"},"sequence":{"accession":"P62306","fasta_url":"https://rest.uniprot.org/uniprotkb/P62306.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P62306/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P62306"}},"corpus_meta":[{"pmid":"32066723","id":"PMC_32066723","title":"A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32066723","citation_count":93,"is_preprint":false},{"pmid":"24383474","id":"PMC_24383474","title":"Genome-wide study of percent emphysema on computed tomography in the general population. 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The cleavage site was mapped near the C-terminus at EEED(81)↓G. The 9-kDa fragment remains associated with U snRNP complexes in apoptotic cells. Caspase-8 and other caspases are implicated in this cleavage. A C-terminally truncated mutant representing the modified form can form an Sm E-F-G complex in vitro that is recognized by anti-Sm patient sera.\",\n      \"method\": \"Caspase inhibitor assays, site-directed mutagenesis, in vitro Sm complex reconstitution, immunoprecipitation with patient anti-Sm sera\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cleavage site mapped by mutagenesis, in vitro reconstitution of truncated Sm E-F-G complex, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"12728255\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"SNRPF (Sm-F) undergoes caspase-mediated cleavage during apoptosis and the U1 snRNP complex (including Sm-F) translocates from its normal nuclear localization to apoptotic bodies near the cell surface during apoptosis. This redistribution may expose modified snRNP components to the immune system.\",\n      \"method\": \"Subcellular fractionation and localization studies of apoptotic cells, biochemical analysis of U1 snRNP complex modifications during apoptosis\",\n      \"journal\": \"The Israel Medical Association journal : IMAJ\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence described, but abstract is a review/summary and does not detail all primary methods; single lab\",\n      \"pmids\": [\"12440236\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Knockdown of UCH-L5 (a deubiquitinase) increases both mRNA and protein levels of SNRPF. UCH-L5 overexpression inhibits glioma cell migration and invasion, and SNRPF-siRNA independently inhibits migration and invasion of U87MG glioma cells, placing SNRPF downstream of UCH-L5 in a pathway regulating glioma cell motility.\",\n      \"method\": \"siRNA knockdown of SNRPF, UCH-L5 knockdown/overexpression, cell migration and invasion assays, mRNA and protein quantification in U87MG/U251 and 293T cells\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via siRNA with defined cellular phenotype (migration/invasion), two cell lines, but single lab and no biochemical mechanism of UCH-L5 acting on SNRPF protein directly\",\n      \"pmids\": [\"29371935\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Mycobacterium tuberculosis secreted protein Rv1435c/hsr1 facilitates direct interaction between Mtb phagosomes and SNRPF (a key spliceosomal snRNP component), disrupting host snRNP biogenesis and causing specific exon-skipping events in host mRNA. Genetic deletion of hsr1 reverses these exon-skipping events, and hsr1-dependent SNRPF staining is observed in infected mouse tissues and human intestinal tuberculosis biopsies.\",\n      \"method\": \"Yeast-2-hybrid screen, in-cell interaction assays, bacterial genetic deletion (Δhsr1), RNA splicing analysis, immunostaining of infected mouse and human tissues\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (Y2H, in-cell assays, genetic deletion with phenotypic rescue, in vivo validation), published in high-impact journal\",\n      \"pmids\": [\"40601628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"SNRPF, a core spliceosomal component, promotes ovarian cancer progression through a feedback loop. SNRPF depletion induces intron 6 retention in DDX24 pre-mRNA, disrupting the Helicase_C domain and generating premature termination codons that activate nonsense-mediated decay (NMD), reducing DDX24 protein. DDX24 depletion similarly promotes intron 2 retention in E2F4, causing NMD-mediated E2F4 downregulation. E2F4 directly binds the SNRPF promoter, forming a self-sustaining SNRPF-DDX24-E2F4 axis. Antisense oligonucleotide-mediated inhibition of SNRPF disrupts this loop and impairs tumor growth in vitro, in vivo, and in patient-derived xenografts.\",\n      \"method\": \"Transcriptomic and proteomic analyses, siRNA knockdown, intron retention analysis, NMD assays, ChIP/promoter binding assays, antisense oligonucleotide treatment, xenograft tumor models including patient-derived xenografts\",\n      \"journal\": \"Advanced science (Weinheim, Baden-Wurttemberg, Germany)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (splicing analysis, NMD validation, promoter binding, in vivo xenograft and PDX), mechanistically defined feedback loop with rescue experiments\",\n      \"pmids\": [\"42107058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"SNRPF binds to the pre-mRNA of TMED2 (transmembrane P24 trafficking protein 2), preventing intron 2 retention and subsequent nonsense-mediated decay, thereby maintaining TMED2 protein abundance. TMED2 in turn directly interacts with cGAS, promoting cGAS activation and downstream STING/TBK1/IRF3 signaling, leading to IFN-β, ISG15, and cytokine production. This SNRPF/TMED2/cGAS-STING axis promotes hepatocellular carcinoma growth and progression.\",\n      \"method\": \"RNA immunoprecipitation, reporter gene assays, co-immunoprecipitation, GST pull-down assays, overexpression/knockdown functional assays, cGAS/STING inhibitor rescue experiments, orthotopic xenograft mouse model\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — RNA immunoprecipitation and GST pull-down establish direct binding, multiple orthogonal methods (RIP, Co-IP, GST pulldown, inhibitor rescue, in vivo orthotopic model), single lab but rigorous\",\n      \"pmids\": [\"41786173\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNRPF (Sm-F) is a core spliceosomal Sm protein that functions within U snRNP complexes to regulate pre-mRNA splicing; it is proteolytically cleaved by caspases (at EEED81↓G) during apoptosis generating a 9-kDa fragment that remains snRNP-associated and relocates to apoptotic bodies, its abundance is regulated downstream of the deubiquitinase UCH-L5 to control glioma cell invasion, it is directly targeted by the M. tuberculosis virulence factor Rv1435c/hsr1 to disrupt host snRNP biogenesis and alter exon usage, it binds TMED2 pre-mRNA to prevent intron retention and NMD thereby activating a TMED2/cGAS-STING oncogenic axis in hepatocellular carcinoma, and it forms a self-sustaining splicing-transcription feedback loop (SNRPF-DDX24-E2F4) in ovarian cancer whereby it prevents intron retention/NMD of DDX24 and E2F4 while E2F4 transcriptionally drives SNRPF expression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNRPF (Sm-F) is a core spliceosomal Sm protein that assembles into U snRNP complexes and governs pre-mRNA splicing fidelity, with emerging roles in apoptosis, host-pathogen interaction, and oncogenesis [#0, #3, #4]. During apoptosis, SNRPF is proteolytically cleaved by caspases at EEED81\\u2193G to yield a 9-kDa fragment that remains associated with U snRNP complexes; concomitantly the U1 snRNP relocates from the nucleus to apoptotic bodies near the cell surface, exposing modified snRNP components recognized by anti-Sm patient sera [#0, #1]. By controlling splice-site selection, SNRPF prevents pathological intron retention in specific transcripts: it binds DDX24 and E2F4 pre-mRNAs to avert intron retention and nonsense-mediated decay, sustaining a self-reinforcing SNRPF-DDX24-E2F4 feedback loop in ovarian cancer, and it binds TMED2 pre-mRNA to maintain TMED2 protein and drive a TMED2/cGAS-STING signaling axis in hepatocellular carcinoma [#4, #5]. SNRPF acts downstream of the deubiquitinase UCH-L5 to promote glioma cell migration and invasion [#2], and it is directly engaged by the M. tuberculosis virulence factor Rv1435c/hsr1, which disrupts host snRNP biogenesis and induces specific exon-skipping events during infection [#3]. Antisense oligonucleotide targeting of SNRPF impairs tumor growth in vitro and in xenograft models, establishing it as a tractable splicing-dependent oncogenic dependency [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established that SNRPF-containing snRNPs are not static during cell death but undergo regulated subcellular redistribution, linking spliceosome components to autoimmune antigen exposure.\",\n      \"evidence\": \"Subcellular fractionation and localization analysis of U1 snRNP in apoptotic cells\",\n      \"pmids\": [\"12440236\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Review-style summary without full primary methods\", \"Mechanism of translocation to apoptotic bodies not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Defined the molecular event behind SNRPF apoptotic modification by mapping a precise caspase cleavage site and showing the cleaved fragment retains snRNP association and antigenicity.\",\n      \"evidence\": \"Caspase inhibitor assays, site-directed mutagenesis of EEED81\\u2193G, in vitro Sm E-F-G reconstitution, IP with anti-Sm patient sera\",\n      \"pmids\": [\"12728255\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional consequence of cleavage for splicing not determined\", \"Which specific caspase is primary in vivo not resolved\", \"Link to autoimmune disease causation not established\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed SNRPF in a cancer cell-motility pathway downstream of a deubiquitinase, the first link of SNRPF abundance to a malignant phenotype.\",\n      \"evidence\": \"siRNA knockdown of SNRPF and UCH-L5, migration/invasion assays in U87MG/U251 glioma cells\",\n      \"pmids\": [\"29371935\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct biochemical mechanism linking UCH-L5 to SNRPF protein\", \"Splicing targets mediating invasion not identified\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed SNRPF as a direct host target of a bacterial virulence factor, showing pathogens can co-opt the spliceosome to remodel host mRNA processing.\",\n      \"evidence\": \"Yeast-2-hybrid, in-cell interaction assays, \\u0394hsr1 genetic deletion with splicing rescue, immunostaining of infected mouse and human biopsies\",\n      \"pmids\": [\"40601628\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional outcome of exon-skipping for infection survival not fully resolved\", \"Structural basis of hsr1-SNRPF interaction unknown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated that SNRPF promotes tumorigenesis through transcript-specific intron-retention control, defining concrete downstream effector axes in two cancer types.\",\n      \"evidence\": \"RNA-IP, intron retention/NMD assays, ChIP promoter binding, Co-IP/GST pull-down, antisense oligonucleotide treatment, orthotopic and patient-derived xenografts\",\n      \"pmids\": [\"42107058\", \"41786173\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether SNRPF selectivity for these transcripts is sequence-specific or context-driven not resolved\", \"Generality of the feedback loops beyond ovarian and hepatocellular carcinoma untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNRPF achieves transcript-selective control of intron retention versus its general role in core spliceosome assembly remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No structural model for SNRPF-pre-mRNA selectivity\", \"Determinants of which introns escape retention upon SNRPF loss undefined\", \"Relationship between caspase cleavage and oncogenic splicing roles unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 4, 5]}\n    ],\n    \"complexes\": [\"U snRNP\", \"U1 snRNP\", \"Sm E-F-G complex\"],\n    \"partners\": [\"TMED2\", \"DDX24\", \"E2F4\", \"Rv1435c/hsr1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}