Affinage

SNRPE

Small nuclear ribonucleoprotein E · UniProt P62304

Round 2 corrected
Length
92 aa
Mass
10.8 kDa
Annotated
2026-04-28
41 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNRPE encodes SmE, a core subunit of the heptameric Sm ring that assembles on spliceosomal U snRNAs and is essential for pre-mRNA splicing. SmE adopts the conserved Sm fold—an N-terminal helix followed by a bent five-stranded antiparallel β-sheet—and participates in ring closure around snRNA, as established by crystal structures of Sm protein complexes (PMID:10025403). SmE directly interacts with the SMN complex during snRNP biogenesis; a disease-causing Phe22Ser mutation abolishes this interaction, preventing U snRNP assembly and causing widespread splicing alterations including mis-splicing of EMX2 (underlying primary microcephaly) and of CTPS1 and FGFR4 in cancer contexts where NMD degrades the aberrant transcripts (PMID:9323129, PMID:31671093, PMID:41933137, PMID:38796598). Heterozygous loss-of-function mutations in SNRPE cause autosomal-dominant hypotrichosis simplex, while the Phe22Ser variant causes non-syndromal primary microcephaly with intellectual disability (PMID:23246290, PMID:31671093).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1990 Medium

    Mapping SNRPE to chromosome 1q32 established its genomic context and distinguished the expressed gene from processed pseudogenes, enabling subsequent mutation screening.

    Evidence Somatic cell hybridization and in situ hybridization in human cell lines

    PMID:2143747

    Open questions at the time
    • Regulatory elements controlling SNRPE expression not characterized
    • No functional data at this stage
  2. 1997 High

    The discovery that SMN directly binds SmE linked snRNP biogenesis to spinal muscular atrophy and established that SmE is a critical interface for the SMN-mediated assembly pathway.

    Evidence Co-immunoprecipitation and direct binding assays in human cells

    PMID:9323129

    Open questions at the time
    • Whether SmE–SMN interaction is essential for snRNP assembly in vivo not yet tested
    • Structural basis of SmE–SMN recognition unknown
  3. 1999 High

    Crystal structures of Sm heterodimers revealed the conserved Sm fold and demonstrated that seven Sm proteins, including SmE, form a closed ring with a positively charged central pore that threads snRNA, providing the architectural basis for snRNP core assembly.

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

    PMID:10025403

    Open questions at the time
    • Full heptameric ring structure with snRNA not yet resolved
    • Dynamics of ring assembly in vivo unknown
  4. 2001 High

    Biochemical dissection of the methylosome pathway showed that SmE participates in pICln-mediated Sm protein channeling to the SMN complex, though SmE itself is not a substrate for symmetric dimethylarginine modification.

    Evidence Co-immunoprecipitation, in vitro methyltransferase assays, and mass spectrometry

    PMID:11713266

    Open questions at the time
    • How SmE is specifically recognized by pICln versus methylated Sm proteins not resolved
    • In vivo consequences of blocking SmE–pICln interaction unknown
  5. 2002 High

    Proteomic identification of SmE in affinity-purified functional spliceosomes confirmed it as a constitutive component present throughout the spliceosome cycle.

    Evidence MBP affinity purification of human spliceosomes followed by nano-LC-MS/MS

    PMID:12226669

    Open questions at the time
    • Whether SmE has spliceosome-specific contacts beyond Sm ring interactions not addressed
  6. 2012 Medium

    Identification of heterozygous SNRPE mutations as the cause of autosomal-dominant hypotrichosis simplex demonstrated that even subtle perturbation of SmE function—without blocking snRNP incorporation—can produce tissue-specific disease, pointing to a splicing-function rather than biogenesis-failure mechanism.

    Evidence Patient sequencing, Western blot, immunofluorescence, and snRNP incorporation assays in HEK293T cells

    PMID:23246290

    Open questions at the time
    • Specific hair follicle splicing targets disrupted by mutant SmE not identified
    • No animal model to confirm causality in vivo
  7. 2019 High

    The Phe22Ser mutation established that SmE–SMN complex interaction is essential for snRNP assembly in human cells and that its disruption causes broad splicing alterations, including EMX2 mis-splicing, which underlies microcephaly—demonstrating a direct genotype-to-phenotype molecular mechanism.

    Evidence Co-IP in patient fibroblasts, RNA-seq splicing analysis, rescue experiments in HEK293 cells, zebrafish morpholino knockdown

    PMID:31671093

    Open questions at the time
    • Whether EMX2 mis-splicing alone is sufficient for microcephaly or additional targets contribute is unclear
    • Structural basis of how Phe22Ser disrupts SMN binding not resolved
  8. 2024 Medium

    In hepatocellular carcinoma, SNRPE loss causes mis-splicing of FGFR4 leading to NMD-mediated transcript degradation, establishing a paradigm where a core spliceosomal factor controls specific oncogenic signaling through splicing fidelity of individual targets.

    Evidence RNA-seq alternative splicing analysis, siRNA knockdown, NMD assays, FGFR4 rescue, and tumor xenograft assays

    PMID:38796598

    Open questions at the time
    • Whether SNRPE overexpression in HCC reflects general snRNP demand or target-specific effects is unresolved
    • No structural or kinetic explanation for why FGFR4 is preferentially affected
  9. 2025 Medium

    Identification of CTPS1 intron 15 retention as the critical splicing defect upon SNRPE loss in ovarian cancer extended the NMD-dependent mechanism to nucleotide metabolism, demonstrating that specific intron-retention events underlie the proliferative consequences of SmE depletion in cancer.

    Evidence RNA-seq splicing analysis, siRNA knockdown, NMD pathway assays, CTPS1 overexpression rescue, in vivo tumor assays

    PMID:41933137

    Open questions at the time
    • What makes CTPS1 and FGFR4 introns particularly sensitive to reduced SmE levels is unknown
    • Whether these splicing vulnerabilities generalize across cancer types not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A central unresolved question is what determines substrate selectivity—why specific pre-mRNAs (EMX2, CTPS1, FGFR4, AR) are preferentially mis-spliced when SmE is reduced, despite SmE being a core spliceosomal component required broadly for splicing.
  • No genome-wide dose–response study relating SmE levels to intron-specific splicing efficiency
  • No structural model of how SmE mutations differentially affect snRNP function on distinct substrates
  • Tissue-specific splicing consequences (e.g., hair follicle vs. brain) remain unexplained at molecular level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-392499 Metabolism of proteins 2
Partners
CLNS1ASMN1SNRPBSNRPD1SNRPD2SNRPD3SNRPFSNRPG
Complex memberships
Sm heptameric ringU1 snRNPU2 snRNPU4/U6.U5 tri-snRNP

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Crystal structures of Sm protein complexes D3B and D1D2 revealed that SmE and other Sm proteins share a common fold with an N-terminal helix followed by a strongly bent five-stranded antiparallel beta sheet, and that the seven Sm proteins could form a closed ring structure through which snRNAs are bound in a positively charged central hole. X-ray crystallography of Sm protein complexes Cell High 10025403
1997 SMN (the spinal muscular atrophy disease gene product) directly interacts with the spliceosomal Sm core protein SmE (SNRPE), forming a complex with SIP1 and multiple snRNP Sm proteins, suggesting a role for SMN in spliceosomal snRNP biogenesis. Co-immunoprecipitation, direct binding assays Cell High 9323129
2001 The methylosome complex (containing JBP1/PRMT5 and pICln) binds Sm proteins via their Sm domains (pICln) and RG-rich domains (JBP1), producing symmetrical dimethylarginine modifications on SmD1 and SmD3 that direct these proteins to the SMN complex for assembly into snRNP core particles; SmE lacks RG-rich domains and is not a methylation substrate but participates in the pICln-Sm interactions. Co-immunoprecipitation, in vitro methyltransferase assay, mass spectrometry Molecular and cellular biology High 11713266
1990 The expressed SNRPE gene (encoding snRNP protein E) was mapped to human chromosome 1q25-43, with most probable location at band 1q32, and identified as a single expressed gene among a multigene family containing processed pseudogenes. Somatic cell hybridization, in situ hybridization, linkage analysis Genomics Medium 2143747
2002 SNRPE was identified as a core spliceosomal protein in affinity-purified, functional human spliceosomes, establishing it as part of the Sm core snRNP proteins present throughout spliceosome assembly. Maltose-binding protein affinity chromatography followed by nanoscale LC-MS/MS Nature High 12226669
2012 Heterozygous mutations in SNRPE (c.1A>G causing loss of start codon, and c.133G>A [p.Gly45Ser]) cause autosomal-dominant hypotrichosis simplex. The c.1A>G mutation produces an N-terminally truncated protein using a downstream start codon. Both mutant proteins localize normally and incorporate into U snRNPs, suggesting the pathogenic mechanism is disruption of U snRNP splicing function rather than biogenesis. Direct sequencing, Western blot, immunofluorescence, snRNP incorporation assay in HEK293T cells American journal of human genetics Medium 23246290
2019 A de novo heterozygous missense mutation in SNRPE (p.Phe22Ser) causes non-syndromal primary microcephaly and intellectual disability. The mutant SmE protein cannot interact with the SMN complex and consequently fails to assemble into U snRNPs, leading to widespread mRNA splicing alterations including mis-splicing of EMX2 (required for brain development). SmE depletion in zebrafish recapitulates aberrant splicing and reduced brain size. Co-immunoprecipitation (SMN complex interaction), RNA-seq (splicing alterations in patient fibroblasts and HEK293 cells), rescue experiments with wild-type vs. mutant SmE, zebrafish knockdown model PLoS genetics High 31671093
2011 SNRPE knockdown by siRNA suppresses prostate cancer cell proliferation and reduces androgen receptor (AR) mRNA expression along with downstream AR target genes; conversely, SNRPE overexpression promotes cell proliferation, establishing that SNRPE regulates AR mRNA expression to support high-grade prostate cancer growth. siRNA knockdown, RT-PCR, cell proliferation assays, overexpression experiments Oncology letters Medium 22740892
2024 SNRPE (activated transcriptionally by SOX2) acts as an oncofetal splicing factor in hepatocellular carcinoma; SNRPE knockdown reduces FGFR4 mRNA levels by triggering nonsense-mediated RNA decay (NMD) of mis-spliced FGFR4 transcripts, and FGFR4 knockdown partially phenocopies SNRPE loss, placing SNRPE upstream of FGFR4 in HCC tumorigenesis. RNA-seq (alternative splicing analysis), siRNA knockdown, NMD assays, in vitro and in vivo tumor assays, FGFR4 rescue experiments British journal of cancer Medium 38796598
2025 In lung adenocarcinoma cells, SNRPE knockdown inhibits proliferation, induces G1 phase arrest, stimulates autophagy, and suppresses ERK/mTOR signaling activation, as evidenced by decreased phospho-ERK and phospho-mTOR and increased LC3B/Beclin1; tumor xenograft growth is also reduced. siRNA knockdown, Western blotting (ERK/mTOR pathway and autophagy markers), CCK-8/colony formation assays, flow cytometry, xenograft mouse model OncoTargets and therapy Low 41268534
2025 SNRPE targeting in breast cancer cells triggers pyroptosis in a ROS-dependent manner, which activates NK cell-mediated antitumor immunity in vivo. siRNA/shRNA knockdown, xenograft murine model, ROS measurement, NK cell cytotoxicity assays International journal of medical sciences Low 40386046
2026 In ovarian cancer, SNRPE deficiency causes intron 15 retention in CTPS1 mRNA, triggering NMD-mediated degradation of unspliced CTPS1 transcripts and reducing functional CTPS1 (the rate-limiting enzyme for CTP synthesis), thereby inducing G1 arrest and apoptosis; CTPS1 overexpression partially rescues SNRPE-knockdown phenotypes. RNA sequencing (splicing analysis), siRNA knockdown, NMD pathway assays, CTPS1 rescue overexpression, in vitro and in vivo tumor assays Oncogene Medium 41933137
1997 Sequence comparison of the SNRPE gene promoter with those of the Sm-D1 gene and U1 snRNA genes revealed several homologous motifs, suggesting that genes encoding snRNP components including SNRPE may be coordinately regulated at the transcriptional level. CAT reporter gene fusion assay, DNA sequencing and promoter sequence comparison Gene Low 9168134

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
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
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
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
1995 Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 660 7566098
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
1997 The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell 569 9323129
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
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
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
1999 Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 374 10025403
2001 The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Molecular and cellular biology 354 11713266
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
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
2013 Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor. Cell reports 307 23403292
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
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2022 EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular cancer 257 35031058
2012 Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex. American journal of human genetics 35 23246290
2011 SNRPE is involved in cell proliferation and progression of high-grade prostate cancer through the regulation of androgen receptor expression. Oncology letters 23 22740892
2019 A missense mutation in SNRPE linked to non-syndromal microcephaly interferes with U snRNP assembly and pre-mRNA splicing. PLoS genetics 20 31671093
2024 Oncofetal SNRPE promotes HCC tumorigenesis by regulating the FGFR4 expression through alternative splicing. British journal of cancer 9 38796598
1990 Assignment of the gene for the small nuclear ribonucleoprotein E (SNRPE) to human chromosome 1q25-q43. Genomics 7 2143747
2024 Impact of potential biomarkers, SNRPE, COX7C, and RPS27, on idiopathic Parkinson's disease. Genes & genomics 4 39467967
2025 Targeting SNRPE to Induce Pyroptosis Enhances Antitumor Immunity in Breast Cancer. International journal of medical sciences 1 40386046
1997 Analysis of genes for human snRNP Sm-D1 protein and identification of the promoter sequence which shows segmental homology to the promoters of Sm-E and U1 snRNA genes. Gene 1 9168134
2026 Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer. Oncogene 0 41933137
2025 SNRPE is Associated with ERK/mTOR Signaling Activation and Reduced Autophagy to Promote Lung Adenocarcinoma Cell Proliferation. OncoTargets and therapy 0 41268534
1991 An EcoO109 RFLP for the SNRPE gene on chromosome 1. Nucleic acids research 0 1674142