Affinage

SNRNP35

U11/U12 small nuclear ribonucleoprotein 35 kDa protein · UniProt Q16560

Round 2 corrected
Length
246 aa
Mass
29.4 kDa
Annotated
2026-04-28
31 papers in source corpus 5 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNRNP35 (U11-35K) is a dedicated component of the minor (U12-dependent) spliceosome that functions in the recognition and splicing of U12-type introns. It associates exclusively with the U11 snRNP and the U11/U12 di-snRNP, where it directly recognizes U11 snRNA; high-resolution cryo-EM structures show that SNRNP35 cooperates with SNRNP48 and U11 snRNA to recognize the U12-type 5′ splice site through a combination of base-pairing and non-canonical base-triple interactions (PMID:38484052, PMID:39809272). Knockdown of SNRNP35 abolishes U12-intron splicing and compromises cell viability, confirming its essential role in the minor splicing pathway (PMID:15146077, PMID:32492425). SNRNP35 expression in the prefrontal cortex is subject to glucocorticoid-mediated downregulation (PMID:32492425).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2004 High

    Identification of SNRNP35 as a novel, U11-specific protein component of the minor spliceosome resolved the protein composition of the 18S U11/U12 di-snRNP and established that it is absent from the major spliceosome.

    Evidence Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout

    PMID:15146077

    Open questions at the time
    • Precise RNA-binding interfaces of SNRNP35 on U11 snRNA were unknown
    • Direct contribution of SNRNP35 to 5′ splice-site recognition had not been tested
    • Mechanism of essentiality (splicing vs. snRNP stability) was not dissected
  2. 2008 Medium

    Demonstrating that minor spliceosome components including SNRNP35 are exclusively nuclear resolved a controversy about putative cytoplasmic minor spliceosome activity.

    Evidence In situ hybridization, subcellular fractionation, and fluorescence microscopy in human cells and mouse tissues

    PMID:18559850

    Open questions at the time
    • Sub-nuclear localization relative to Cajal bodies or speckles was not resolved
    • Whether SNRNP35 shuttles during snRNP biogenesis was not addressed
  3. 2020 Medium

    Functional knockdown of SNRNP35 confirmed its requirement for U12-intron splicing and revealed that its expression is regulated by glucocorticoids in the brain, linking minor spliceosome biology to stress-responsive gene regulation.

    Evidence siRNA knockdown with U12-intron splicing assay; qPCR in glucocorticoid-treated mouse prefrontal cortex; gene expression analysis in human leukocytes after deployment stress

    PMID:32492425

    Open questions at the time
    • The mechanism by which glucocorticoids regulate SNRNP35 transcription (direct GR binding vs. indirect pathway) was not defined
    • Whether glucocorticoid-driven SNRNP35 reduction selectively impairs specific U12-intron-containing transcripts was not established
  4. 2024 High

    The cryo-EM structure of the minor spliceosome pre-B complex revealed, at atomic resolution, that SNRNP35 is one of five U11-specific proteins recognizing U11 snRNA and that it cooperates with SNRNP48 and U11 snRNA to engage the 5′ half of the 5′ splice site.

    Evidence Cryo-EM at 3.3 Å resolution with atomic model building of the human pre-B complex

    PMID:38484052

    Open questions at the time
    • Conformational changes in SNRNP35 upon catalytic activation were not captured
    • Mutational validation of predicted SNRNP35–RNA contacts was not performed
  5. 2025 High

    Structures of the apo and substrate-bound U11 snRNP showed that SNRNP35 specifically recognizes U11 snRNA, while SNRNP48 and ZMAT5 stabilize 5′SS binding through base-pairing and non-canonical base-triple interactions, completing the mechanistic picture of initial 5′ splice-site recognition.

    Evidence Cryo-EM reconstruction of 13-subunit human U11 snRNP in apo and substrate-bound states

    PMID:39809272

    Open questions at the time
    • How SNRNP35 is released or repositioned during the transition from U11 snRNP to activated spliceosome is unknown
    • Whether disease-associated variants in SNRNP35 disrupt its snRNA-binding interface has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether SNRNP35 loss differentially affects specific subsets of U12-intron-containing genes in a tissue-specific manner, and the structural basis for its glucocorticoid-mediated transcriptional regulation is undefined.
  • Tissue-specific phenotypic consequences of SNRNP35 deficiency have not been characterized in animal models
  • No direct promoter-level mechanism for glucocorticoid regulation of SNRNP35 has been identified
  • No human Mendelian disease has been linked to SNRNP35 mutations

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
PDCD7SNRNP25SNRNP48ZMAT5
Complex memberships
U11 snRNPU11/U12 di-snRNP

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SNRNP35 (35K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP complex and the 12S U11 snRNP, absent from the major (U2-dependent) spliceosome. It was found to be U11-associated and is highly conserved in organisms containing U12-type introns. RNAi knockdown of U11/U12 proteins including 35K revealed essential roles in cell viability, indicating key functions in U12-type splicing. Affinity purification of human U11/U12 and U11 snRNPs followed by mass spectrometry identification; RNAi knockdown with cell viability readout RNA (New York, N.Y.) High 15146077
2008 SNRNP35, as a component of the minor spliceosome U11/U12 snRNP, is predominantly localized in the nucleus. Subcellular fractionation and in situ hybridization in mouse tissues and human cells showed that minor spliceosome components (snRNAs and proteins) are nuclear, colocalizing with major spliceosome components, refuting earlier claims of cytoplasmic minor spliceosome activity. In situ hybridization, subcellular fractionation of human cells, fluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America Medium 18559850
2020 SNRNP35 knockdown in cells validated its functional role in U12-intron splicing. Additionally, SNRNP35 expression in dorsolateral prefrontal cortex is regulated by glucocorticoids: exogenous glucocorticoids downregulate prefrontal Snrnp35 in mice, and deployment stress in marines produces downregulation of SNRNP35 consistent with glucocorticoid-regulated expression. siRNA knockdown with U12-intron splicing assay readout; qPCR in mouse model with glucocorticoid treatment; gene expression correlation in human peripheral leukocytes Cell reports Medium 32492425
2024 Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex (3.3 Å) revealed that U11 snRNA is recognized by five U11-specific proteins including U11-35K (SNRNP35). The 3′ half of the 5′-splice site forms a duplex with U11 snRNA, while the 5′ half is recognized cooperatively by U11-35K, U11-48K, and U11 snRNA. Cryo-electron microscopy structure determination at 3.3 Å resolution; atomic model building Science (New York, N.Y.) High 38484052
2025 Cryo-EM reconstruction of the 13-subunit human U11 snRNP in apo and substrate-bound forms revealed that SNRNP35 specifically recognizes U11 snRNA. PDCD7 bridges SNRNP25 and SNRNP48 at the distal ends of the particle, while SNRNP48 and ZMAT5 stabilize binding of the incoming 5′ splice site. Recognition of the U12-type 5′SS is achieved through base-pairing to the 5′ end of U11 snRNA and non-canonical base-triple interactions with U11 snRNA stem-loop 3. Cryo-electron microscopy reconstruction of apo and substrate-bound U11 snRNP; structural analysis of protein-RNA and protein-protein contacts Molecular cell High 39809272

Source papers

Stage 0 corpus · 31 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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2014 Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Proceedings of the National Academy of Sciences of the United States of America 167 25201988
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2004 The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome. RNA (New York, N.Y.) 128 15146077
2011 Toxicogenomic and phenotypic analyses of bisphenol-A early-life exposure toxicity in zebrafish. PloS one 93 22194820
2009 Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis and rheumatism 90 19565553
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2018 RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease. The Journal of biological chemistry 65 29802200
2005 Major conformational change in the complex SF3b upon integration into the spliceosomal U11/U12 di-snRNP as revealed by electron cryomicroscopy. Molecular cell 65 15780942
2020 Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell reports 52 32492425
2020 RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation. Proceedings of the National Academy of Sciences of the United States of America 47 32513696
2021 Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer. Nature communications 36 34373451
2021 An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity. Cell chemical biology 35 34672954
2008 Minor spliceosome components are predominantly localized in the nucleus. Proceedings of the National Academy of Sciences of the United States of America 34 18559850
2024 Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome. Science (New York, N.Y.) 20 38484052
2011 Site-directed mutagenesis of the CC chemokine binding protein 35K-Fc reveals residues essential for activity and mutations that increase the potency of CC chemokine blockade. Molecular pharmacology 16 21586597
2022 TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells. Biochemical and biophysical research communications 9 35944360
2024 DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples. Journal of proteome research 7 38334954
2023 Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library. Pharmacogenomics and personalized medicine 7 36743888
2025 Structural basis of 5' splice site recognition by the minor spliceosome. Molecular cell 6 39809272
1998 Cloning and characterization of a family of cDNAs from human histiocyte macrophage cells encoding an arginine-rich basic protein related to the 70 kD U1-snRNP splicing factor. DNA sequence : the journal of DNA sequencing and mapping 1 10520751