Affinage

SNRPF

Small nuclear ribonucleoprotein F · UniProt P62306

Round 2 corrected
Length
86 aa
Mass
9.7 kDa
Annotated
2026-04-28
60 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNRPF (SmF) is a core Sm protein of the spliceosome that assembles with six other Sm proteins into a heptameric ring around snRNAs, functioning as an essential structural and functional component of U snRNP biogenesis and pre-mRNA splicing (PMID:10025403, PMID:12226669, PMID:11991638). The Sm ring is assembled in the cytoplasm with assistance from the SMN complex, and SNRPF resides predominantly in the nucleus where it participates in spliceosomal catalysis (PMID:10601333, PMID:35271311). During apoptosis, SNRPF is cleaved by caspases at EEED81↓G, generating a truncated fragment that remains snRNP-associated and serves as an autoantigen recognized by anti-Sm sera from systemic lupus erythematosus patients (PMID:12728255, PMID:12440236). Beyond housekeeping splicing, SNRPF is directly targeted by the Mycobacterium tuberculosis virulence factor Rv1435c/hsr1 at phagosomes to subvert host snRNP biogenesis and splicing (PMID:40601628), and in hepatocellular carcinoma it regulates TMED2 pre-mRNA splicing to maintain TMED2 abundance and activate cGAS-STING/TBK1/IRF3 inflammatory signaling (PMID:41786173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 High

    Determining the structural basis of Sm protein assembly resolved how SmF and its partners fold into a ring that encircles snRNA, establishing the architectural framework for all downstream snRNP biology.

    Evidence X-ray crystallography of D3B and D1D2 Sm protein complexes

    PMID:10025403

    Open questions at the time
    • Structure of the complete heptameric ring with snRNA was not resolved in this study
    • Individual contributions of SmF interfaces to ring stability were not dissected
  2. 1999 Medium

    Establishing that the SMN complex interacts with Sm proteins in the cytoplasm defined the biogenesis pathway through which SmF is loaded onto snRNAs before nuclear import.

    Evidence Co-immunoprecipitation, yeast two-hybrid, and immunofluorescence in human cells

    PMID:10601333

    Open questions at the time
    • Direct SmF–Gemin3 or SmF–SMN binary interaction was not separately demonstrated
    • Kinetic order of Sm protein loading onto snRNA not resolved
  3. 2002 High

    Proteomic identification of SmF within purified, functional human spliceosomes confirmed its role as a bona fide catalytic-complex component, not merely a biogenesis intermediate.

    Evidence Affinity purification of active spliceosomes followed by nanoscale LC-MS/MS (two independent studies)

    PMID:11991638 PMID:12226669

    Open questions at the time
    • SmF's contacts within distinct spliceosomal conformational states (B, C, etc.) were not individually mapped
  4. 2003 High

    Mapping caspase-mediated cleavage of SmF at EEED81↓G during apoptosis and showing the truncated fragment remains snRNP-associated and is recognized by lupus anti-Sm sera linked SmF processing to autoantigen generation in SLE.

    Evidence Caspase inhibitor studies, mutagenesis, in vitro Sm E-F-G reconstitution, immunoprecipitation with patient sera; complemented by apoptotic body localization studies

    PMID:12440236 PMID:12728255

    Open questions at the time
    • Whether the cleaved SmF fragment has altered snRNP function beyond serving as an autoantigen is unknown
    • In vivo evidence that caspase-cleaved SmF is the initiating autoantigen in SLE has not been established
  5. 2012 Medium

    Systematic mapping of spliceosomal protein–protein interactions placed SmF within a broader interaction wiring diagram, revealing its dynamic contacts during the splicing cycle.

    Evidence Yeast two-hybrid matrix screen with co-immunoprecipitation validation

    PMID:22365833

    Open questions at the time
    • Temporal resolution of SmF interaction changes across spliceosome assembly states was not achieved
    • Functional consequences of disrupting individual SmF interactions were not tested
  6. 2017 Medium

    Discovery that SNRPF knockdown inhibits glioma cell migration and invasion, with UCH-L5 acting as an upstream negative regulator, revealed a non-canonical role for SmF in tumor cell behavior.

    Evidence siRNA knockdown in U87MG and U251 glioma lines; UCH-L5 knockdown in 293T cells; migration/invasion assays

    PMID:29371935

    Open questions at the time
    • The specific ubiquitin-dependent mechanism by which UCH-L5 suppresses SNRPF is not defined
    • Whether the migration phenotype is splicing-dependent or reflects a moonlighting function is unclear
    • Single-laboratory finding without independent replication
  7. 2022 Medium

    Identification of SNRPF in stress granules by proximity labeling and confirmation of its nuclear localization by endogenous tagging expanded its known compartmentalization beyond steady-state nuclear residence.

    Evidence BioID proximity-dependent biotinylation proteomics; endogenous GFP tagging with confocal live-cell imaging

    PMID:29395067 PMID:35271311

    Open questions at the time
    • Functional role of SmF in stress granules (structural vs. regulatory) is unknown
    • Conditions driving SmF redistribution to cytoplasmic granules not characterized
  8. 2025 High

    Demonstration that the M. tuberculosis virulence factor hsr1 directly binds SNRPF at phagosomes to disrupt snRNP biogenesis and host splicing established SmF as a pathogen-targeted node exploited for immune evasion.

    Evidence Yeast two-hybrid, in-cell interaction assays, Δhsr1 genetic deletion, RNA splicing analysis, mouse and human infection models

    PMID:40601628

    Open questions at the time
    • Structural basis of the hsr1–SNRPF interaction is not resolved
    • Whether hsr1 disrupts the Sm ring or blocks SMN-mediated assembly is not distinguished
  9. 2026 High

    Showing that SNRPF binds TMED2 pre-mRNA to prevent intron retention and nonsense-mediated decay, thereby sustaining cGAS-STING/TBK1/IRF3 signaling, established a direct mechanistic link between SmF-mediated splicing regulation and innate immune activation in hepatocellular carcinoma.

    Evidence RNA immunoprecipitation, Co-IP, GST pull-down, rescue with cGAS/STING inhibitors, orthotopic xenograft model

    PMID:41786173

    Open questions at the time
    • Whether SNRPF binding to TMED2 pre-mRNA reflects a general splicing function or a specific regulatory interaction is not resolved
    • Relevance of the SNRPF/TMED2/cGAS axis beyond HCC is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how SmF's core spliceosomal function is mechanistically connected to its emerging roles in stress granule biology, pathogen-driven splicing subversion, and tumor-specific splicing regulation — whether these reflect general splicing perturbation or SmF-specific moonlighting.
  • No separation-of-function mutants distinguish SmF's core snRNP role from its disease-related activities
  • Complete structural model of SmF within a fully assembled spliceosome is lacking
  • Transcriptome-wide identification of SmF-dependent splicing events has not been performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
SMN1SNRPBSNRPD1SNRPD2SNRPD3SNRPESNRPGTMED2
Complex memberships
Sm ring (heptameric Sm core)Spliceosome (C complex)U1 snRNPU5 snRNP

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Crystal structures of two Sm protein complexes (D3B and D1D2) revealed that Sm proteins, including SmF (SNRPF), share a common fold consisting of an N-terminal helix followed by a strongly bent five-stranded antiparallel beta sheet. The structures suggest that the seven Sm proteins form a closed ring, with snRNAs bound in the positively charged central hole. X-ray crystallography of Sm protein complexes Cell High 10025403
2002 SNRPF (SmF) was identified as a core component of the spliceosome by comprehensive proteomic analysis of purified, functional human spliceosomes, confirming its presence in the macromolecular splicing machinery. Maltose-binding protein affinity chromatography followed by nanoscale LC-MS/MS proteomics of purified spliceosomes Nature High 12226669
2002 SNRPF (SmF) was identified as a core snRNP protein in affinity-purified native C-complex spliceosomes, along with other SM and LSM proteins, U2 and U5 snRNP-specific proteins, and second-step factors. Native affinity purification of spliceosomes with size exclusion chromatography and tandem mass spectrometry RNA High 11991638
2003 During apoptosis, the Sm-F protein (SNRPF) is proteolytically cleaved by caspases, generating a 9-kDa C-terminal fragment. The cleavage site was mapped near the C-terminus at EEED(81)↓G. The truncated fragment remains associated with U snRNP complexes in apoptotic cells, and caspase-8 and other caspases are implicated. A C-terminally truncated mutant can still form an Sm E-F-G complex in vitro and is recognized by anti-Sm patient sera. Western blot of apoptotic cell extracts, caspase inhibitor studies, site-directed cleavage site mapping, in vitro Sm complex reconstitution, immunoprecipitation with patient sera Cell death and differentiation High 12728255
2002 The U1 snRNP complex, including the Sm-F protein (SNRPF), undergoes caspase-mediated cleavage and translocates from its normal nuclear localization to apoptotic bodies near the cell surface during apoptosis, potentially exposing modified autoantigens to the immune system. Cell biology and immunological analysis of apoptotic cells; subcellular fractionation and localization studies The Israel Medical Association journal : IMAJ Medium 12440236
1999 Gemin3 (a DEAD box helicase in the SMN complex) interacts directly with SmB, SmD2, and SmD3; the SMN complex interacts with Sm core proteins of spliceosomal snRNPs including SmF (SNRPF) in the cytoplasm and plays a critical role in snRNP assembly. Immunolocalization, co-immunoprecipitation, yeast two-hybrid, immunofluorescence The Journal of cell biology Medium 10601333
2012 SNRPF protein interactions within the human spliceosome were systematically mapped; 242 interactions between spliceosomal core proteins including SNRPF were identified and largely validated by co-immunoprecipitation, revealing dynamic protein-protein interaction wiring during splicing. Yeast two-hybrid interaction matrix screen with co-immunoprecipitation validation Molecular cell Medium 22365833
2017 SNRPF knockdown by siRNA inhibited migration and invasion of glioma cells (U87MG and U251). UCH-L5 (a deubiquitinase) suppresses SNRPF expression, and knockdown of UCH-L5 increased both mRNA and protein levels of SNRPF; this relationship was confirmed in 293T cells, establishing UCH-L5 as a negative upstream regulator of SNRPF that operates through ubiquitin-mediated mechanisms. siRNA knockdown, Western blot, qRT-PCR, migration/invasion assays, co-expression analysis in glioma cell lines and 293T cells Oncotarget Medium 29371935
2025 The Mycobacterium tuberculosis secreted protein Rv1435c/hsr1 directly interacts with SNRPF and U5 snRNA at Mtb phagosomes, disrupting host snRNP biogenesis and causing specific exon-skipping events. Genetic deletion of hsr1 reverses these splicing alterations and compromises Mtb growth in macrophages and mice. SNRPF staining in tissue sections was hsr1-dependent, observed in both mouse infection and human intestinal tuberculosis biopsies. Yeast two-hybrid screen, in-cell interaction assays, RNA splicing analysis, genetic deletion (Δhsr1 strain), ex vivo and in vivo infection models, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 40601628
2026 SNRPF promotes hepatocellular carcinoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistically, SNRPF binds to the pre-mRNA of TMED2, preventing intron 2 retention and nonsense-mediated decay, thereby maintaining TMED2 protein abundance. TMED2 in turn directly interacts with cGAS (shown by Co-IP and GST pull-down), promoting cGAS activation and downstream STING/TBK1/IRF3 signaling, leading to IFN-β, ISG15, IFIT1/2, TNF-α, and IL-6 induction. The SNRPF/TMED2/cGAS-STING axis was confirmed in an orthotopic xenograft tumor model. RNA immunoprecipitation, reporter gene assays, Co-immunoprecipitation, GST pull-down, siRNA knockdown, overexpression, rescue experiments with cGAS/STING inhibitors, orthotopic xenograft mouse model International journal of biological macromolecules High 41786173
2022 SNRPF was identified as a core component of stress granules by high-density proximity mapping (BioID) of mRNA-associated granule proteins in human cells. BioID proximity-dependent biotinylation proteomics in human cells Molecular cell Medium 29395067
2022 SNRPF was localized to the nucleus in human cells by endogenous GFP tagging combined with confocal live-cell imaging, and identified as part of the spliceosomal interaction network by co-immunoprecipitation mass spectrometry. Genome engineering (endogenous GFP tagging), confocal live-cell imaging, mass spectrometry-based interaction mapping Science Medium 35271311

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2002 Comprehensive proteomic analysis of the human spliceosome. Nature 725 12226669
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2011 IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nature immunology 405 21642987
2011 Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 405 22020285
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
1999 Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 374 10025403
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2003 Splicing double: insights from the second spliceosome. Nature reviews. Molecular cell biology 329 14685174
2012 Dynamic protein-protein interaction wiring of the human spliceosome. Molecular cell 318 22365833
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2002 Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA (New York, N.Y.) 301 11991638
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2002 Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein. The EMBO journal 237 12234937
1999 Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. The Journal of cell biology 235 10601333
2020 A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy. Nature communications 91 32066723
2012 Impact of maternal aging on the molecular signature of human cumulus cells. Fertility and sterility 84 22968048
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 83 24383474
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
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
2017 Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell migration and invasion via downregulating SNRPF. Oncotarget 13 29371935
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 5 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 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 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 2 41014671
2024 JAK and STAT5B mediate olfactory response of migratory locusts to their own volatiles. Insect biochemistry and molecular biology 2 39068995
2024 DNA barcoding, micromorphology and metabolic traits of selected Ficus L. (Moraceae) species from Egypt. BMC plant biology 2 39538137
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
2025 Construction and differential analysis of testicular atlas between 10-week-old and 23-week-old ducks using single-cell RNA sequencing. Poultry science 0 40884870
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