Affinage

SNRPF

Small nuclear ribonucleoprotein F · UniProt P62306

Length
86 aa
Mass
9.7 kDa
Annotated
2026-06-10
32 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2002 Medium

    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

    PMID:12440236

    Open questions at the time
    • Review-style summary without full primary methods
    • Mechanism of translocation to apoptotic bodies not defined
    • Single lab
  2. 2003 High

    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

    PMID:12728255

    Open questions at the time
    • Functional consequence of cleavage for splicing not determined
    • Which specific caspase is primary in vivo not resolved
    • Link to autoimmune disease causation not established
  3. 2017 Medium

    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

    PMID:29371935

    Open questions at the time
    • No direct biochemical mechanism linking UCH-L5 to SNRPF protein
    • Splicing targets mediating invasion not identified
    • Single lab
  4. 2025 High

    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

    PMID:40601628

    Open questions at the time
    • Functional outcome of exon-skipping for infection survival not fully resolved
    • Structural basis of hsr1-SNRPF interaction unknown
  5. 2026 High

    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

    PMID:41786173 PMID:42107058

    Open questions at the time
    • 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

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SNRPF achieves transcript-selective control of intron retention versus its general role in core spliceosome assembly remains unresolved.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 3
Partners
DDX24E2F4RV1435C/HSR1TMED2
Complex memberships
Sm E-F-G complexU snRNPU1 snRNP

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 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. Caspase inhibitor assays, site-directed mutagenesis, in vitro Sm complex reconstitution, immunoprecipitation with patient anti-Sm sera Cell death and differentiation High 12728255
2002 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. Subcellular fractionation and localization studies of apoptotic cells, biochemical analysis of U1 snRNP complex modifications during apoptosis The Israel Medical Association journal : IMAJ Medium 12440236
2017 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. siRNA knockdown of SNRPF, UCH-L5 knockdown/overexpression, cell migration and invasion assays, mRNA and protein quantification in U87MG/U251 and 293T cells Oncotarget Medium 29371935
2025 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. Yeast-2-hybrid screen, in-cell interaction assays, bacterial genetic deletion (Δhsr1), RNA splicing analysis, immunostaining of infected mouse and human tissues Proceedings of the National Academy of Sciences of the United States of America High 40601628
2026 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. 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 Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 42107058
2026 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. RNA immunoprecipitation, reporter gene assays, co-immunoprecipitation, GST pull-down assays, overexpression/knockdown functional assays, cGAS/STING inhibitor rescue experiments, orthotopic xenograft mouse model International journal of biological macromolecules High 41786173

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy. Nature communications 93 32066723
2014 Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study. American journal of respiratory and critical care medicine 85 24383474
2012 Impact of maternal aging on the molecular signature of human cumulus cells. Fertility and sterility 84 22968048
2020 Exploring Shared Pathogenesis of Alzheimer's Disease and Type 2 Diabetes Mellitus via Co-expression Networks Analysis. Current Alzheimer research 30 32781959
2013 Low-molecular-mass secretome profiling identifies C-C motif chemokine 5 as a potential plasma biomarker and therapeutic target for nasopharyngeal carcinoma. Journal of proteomics 30 24080422
2016 Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 27623942
2010 Combined measurement of soluble and cellular ICAM-1 among children with Plasmodium falciparum malaria in Uganda. Malaria journal 21 20712868
2020 Proteomic Characterization of Proliferation Inhibition of Well-Differentiated Laryngeal Squamous Cell Carcinoma Cells Under Below-Background Radiation in a Deep Underground Environment. Frontiers in public health 18 33194991
2020 Comparing PCR techniques against conventional cercarial shedding methods for detecting Schistosoma mansoni infection in Biomphalaria snails. Acta tropica 16 32966841
2017 Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell migration and invasion via downregulating SNRPF. Oncotarget 15 29371935
2002 The fate of the U1 snRNP autoantigen during apoptosis: implications for systemic autoimmunity. The Israel Medical Association journal : IMAJ 15 12440236
2003 Caspase-mediated cleavage of the U snRNP-associated Sm-F protein during apoptosis. Cell death and differentiation 14 12728255
2018 Proteomics of Bulked Rachides Combined with Documented QTL Uncovers Genotype Nonspecific Players of the Fusarium Head Blight Responses in Wheat. Phytopathology 13 30040027
2023 Genes whose expressions in the primary lung squamous cell carcinoma are able to accurately predict the progression of metastasis through lymphatic system, inferred from a bioinformatics analyses. Scientific reports 12 37185598
2022 Comprehensive transcriptomics and proteomics analysis of Carassius auratus gills in response to Aeromonas hydrophila. Fish and shellfish immunology reports 12 36589261
2023 Newcastle Disease Virus (NDV)-based vaccine candidate against SARS-CoV-2 Omicron by intranasal immunization. Antiviral research 6 37984567
2022 Pseudogene SNRPFP1 derived long non-coding RNA facilitates hepatocellular carcinoma progress in vitro by sponging tumor-suppressive miR-126-5p. Scientific reports 6 36535956
2020 Genetic variants entail type 2 diabetes as an innate immune disorder. Biochimica et biophysica acta. Proteins and proteomics 5 32474106
2020 About three-fourths of mouse proteins unexpectedly appear at a low position of SDS-PAGE, often as additional isoforms, questioning whether all protein isoforms have been eliminated in gene-knockout cells or organisms. Protein science : a publication of the Protein Society 4 31930537
2012 Evaluation of BTA1 and BTA5 QTL Regions for Growth and Carcass Traits in American and Korean Cattle. Asian-Australasian journal of animal sciences 4 25049512
2025 Integrating metagenomics, lipidomics and proteomics to explore the effect and mechanism of ginsenoside Rb1 on atherosclerosis co-depression disease. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 41014671
2024 DNA barcoding, micromorphology and metabolic traits of selected Ficus L. (Moraceae) species from Egypt. BMC plant biology 3 39538137
2025 A Mycobacterium tuberculosis secreted virulence factor Rv1435c/hsr1 disrupts host snRNP biogenesis. Proceedings of the National Academy of Sciences of the United States of America 2 40601628
2025 Construction and differential analysis of testicular atlas between 10-week-old and 23-week-old ducks using single-cell RNA sequencing. Poultry science 2 40884870
2024 JAK and STAT5B mediate olfactory response of migratory locusts to their own volatiles. Insect biochemistry and molecular biology 2 39068995
2026 Integrating plasma proteomes with genome-wide association data for causal protein identification in hepatocellular carcinoma: A bidirectional Mendelian randomization study. Medicine 0 41578465
2026 Promotion of hepatocellular carcinoma by small nuclear ribonucleoprotein polypeptide F through upregulation of transmembrane P24 trafficking protein 2 and triggering of the cGAS-STING pathway. International journal of biological macromolecules 0 41786173
2026 Disruption of the SNRPF-DDX24-E2F4 Feedback Loop Uncouples Splicing and Transcriptional Regulation to Suppress Ovarian Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42107058
2026 Comparison of Sertoli cells in duck testes pre- and post-sexual maturation. Poultry science 0 42190478
2025 Genetic Diversity and Infection Prevalence of Biomphalaria pfeifferi (Krauss, 1848), the Intermediate Snail Host of Schistosoma mansoni in Gezira State, Sudan. International journal of molecular sciences 0 41096832
2024 Transcriptional genes of lysosome-associated membrane protein 2A in sciatic nerve injuries by bioinformatics. Neuroreport 0 38935077
2012 [Genetic diversity of ATP synthase cab subunits amplified from Streptococcus mutans clinical isolates from Uyghur children with different caries susceptibility]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 0 23141730

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