Affinage

SNRNP48

U11/U12 small nuclear ribonucleoprotein 48 kDa protein · UniProt Q6IEG0

Round 2 corrected
Length
339 aa
Mass
40.0 kDa
Annotated
2026-04-28
32 papers in source corpus 5 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNRNP48 (U11-48K) is a U11 snRNP-specific protein of the minor (U12-dependent) spliceosome that is essential for recognition of U12-type 5' splice sites and cell viability (PMID:15146077, PMID:18347052). Its CHHC zinc-finger domain, structurally related to TFIIIA-type zinc fingers, directly contacts the 5' splice site sequence in a sequence-dependent manner and stabilizes U11 snRNA–5'SS base-pairing (PMID:19217400, PMID:18347052). Within the U11 snRNP particle, SNRNP48 is bridged to SNRNP25 via PDCD7 and cooperates with U11-35K and ZMAT5 in 5'SS recognition through canonical base-pairing and non-canonical base-triple interactions with U11 snRNA stem-loop 3 (PMID:38484052, PMID:39809272). Depletion of SNRNP48 inhibits U12-type splicing, activates cryptic U2-type splice sites, and destabilizes the U11/U12 di-snRNP (PMID:18347052).

Mechanistic history

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

    Establishing the molecular identity of minor spliceosome-specific subunits resolved which proteins are dedicated to U12-type splicing: SNRNP48 was identified as one of four U11 snRNP-specific proteins absent from the major spliceosome, and knockdown showed it is required for cell viability.

    Evidence Affinity purification of human U11/U12 di-snRNP followed by mass spectrometry and RNAi-mediated knockdown with viability readout

    PMID:15146077

    Open questions at the time
    • Molecular function of SNRNP48 within the U11 particle was unknown
    • Direct RNA contacts had not been mapped
    • Whether SNRNP48 loss specifically impairs U12-type splicing or has broader effects was not distinguished
  2. 2008 High

    Defining how the minor spliceosome recognizes U12-type 5' splice sites, cross-linking demonstrated that SNRNP48 directly and sequence-dependently contacts the 5'SS, interacts with U11-59K, and is required for U12-type intron splicing and U11/U12 di-snRNP stability.

    Evidence Site-specific RNA-protein cross-linking, co-immunoprecipitation, and RNAi knockdown with RT-PCR splicing assays in human cells

    PMID:18347052

    Open questions at the time
    • The structural basis for sequence-dependent 5'SS recognition was not resolved
    • Whether 48K recognizes the 5'SS alone or cooperatively with other subunits was unclear
  3. 2009 High

    Determining how the SNRNP48 CHHC zinc-finger domain achieves RNA recognition, NMR structure determination revealed an unexpected TFIIIA-type fold that specifically binds the U11 snRNA–5'SS duplex, establishing this domain as the structural basis for stabilizing splice-site base-pairing.

    Evidence NMR solution structure of the CHHC zinc-finger domain and in vitro RNA binding assays with U12-type 5'SS sequences

    PMID:19217400

    Open questions at the time
    • How this interaction is positioned within the intact U11 snRNP particle was unknown
    • Contribution of other U11 proteins to cooperative 5'SS recognition was not addressed
  4. 2024 High

    Placing SNRNP48 into the architectural context of an assembled minor spliceosome, the cryo-EM structure of the pre-B complex showed that U11-48K, together with U11-35K and U11 snRNA, jointly recognizes the 5' half of the 5' splice site at atomic resolution.

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

    PMID:38484052

    Open questions at the time
    • The apo-state architecture of U11 snRNP before substrate engagement was not captured
    • The role of PDCD7 in organizing the U11 particle was not resolved
  5. 2025 High

    Resolving the complete U11 snRNP in both apo and substrate-bound states clarified that SNRNP48 is positioned near the 5' end of U11 snRNA, is bridged to SNRNP25 by PDCD7, and cooperates with ZMAT5 in 5'SS recognition through non-canonical base-triple interactions with U11 snRNA stem-loop 3.

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

    PMID:39809272

    Open questions at the time
    • Conformational dynamics of SNRNP48 during spliceosome activation and catalysis are not captured
    • How disease-associated mutations in minor spliceosome genes affect SNRNP48 function is unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how SNRNP48's interactions are remodeled during the transition from early U11 recognition to catalytic activation of U12-type introns, and whether SNRNP48 participates in regulatory discrimination among U12-type substrates.
  • No structural data for SNRNP48 in activated or catalytic spliceosome states
  • Potential regulatory roles in alternative splicing of U12-type introns are uncharacterized
  • No in vivo structure–function analysis of the CHHC zinc-finger domain

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0005198 structural molecule activity 3
Localization
GO:0005654 nucleoplasm 3
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
PDCD7RNPC3SNRNP25SNRNP35ZMAT5
Complex memberships
Minor spliceosome (pre-B complex)U11 snRNPU11/U12 di-snRNP

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SNRNP48 (U11-48K) was identified as a novel protein component of the human 18S U11/U12 di-snRNP and 12S U11 snRNP, not found in the major spliceosome. Mass spectrometry analysis showed it is one of four proteins (59K, 48K, 35K, 25K) specifically associated with the U11 snRNP within the di-snRNP complex. RNAi knockdown of U11/U12 proteins including 48K revealed they are essential for cell viability, indicating a key role in U12-type splicing. Affinity purification of U11/U12 snRNPs followed by mass spectrometry; RNAi knockdown with cell viability readout RNA (New York, N.Y.) High 15146077
2008 SNRNP48 (U11-48K) directly contacts the 5' splice site (5'ss) of U12-type introns via site-specific RNA-protein cross-linking. This interaction is sequence-dependent and sensitive to 5'ss mutations. 48K also interacts with the U11-59K protein. RNAi-mediated knockdown of 48K inhibited U12-type splicing, activated cryptic U2-type splice sites, reduced cell growth, and decreased U11/U12 di-snRNP levels, indicating 48K is critical for U12-type intron recognition and di-snRNP stability. Site-specific RNA-protein cross-linking; RNAi knockdown with splicing assays and cell growth readouts; co-immunoprecipitation for protein-protein interaction Molecular and cellular biology High 18347052
2009 The solution structure of the SNRNP48 (U11-48K) CHHC zinc-finger domain was determined by NMR. The domain shows unexpected structural similarity to TFIIIA-type zinc fingers, with distinct features from its zinc-coordinating residues (CHHC). The CHHC Zn-finger specifically binds the 5' splice site sequence of U12-type introns when base-paired to U11 snRNA in vitro, suggesting it stabilizes U11–5'ss base-pairing and contributes to minor spliceosome assembly. NMR solution structure determination; in vitro RNA binding assay with U12-type 5'ss sequences Structure (London, England : 1993) High 19217400
2024 Cryo-EM structure of the fully assembled human minor spliceosome pre-B complex at 3.3 Å resolution revealed that U11 snRNA is recognized by five U11-specific proteins including SNRNP48 (U11-48K). The 5' half of the 5'-splice site is recognized jointly by U11-35K, U11-48K, and U11 snRNA, providing structural detail of 5'ss recognition within the assembled minor spliceosome. Cryo-electron microscopy (3.3 Å resolution) with 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 SNRNP48 is positioned near the 5' end of U11 snRNA and stabilizes binding of the incoming U12-type 5' splice site. PDCD7 bridges SNRNP25 and SNRNP48, which are located at distal ends of the particle. SNRNP48 and ZMAT5 together participate in 5'SS recognition, which is achieved through base-pairing to 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 Molecular cell High 39809272

Source papers

Stage 0 corpus · 32 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
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
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
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
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2003 The DNA sequence and analysis of human chromosome 6. Nature 242 14574404
2009 Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. Journal of virology 176 19640993
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
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
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
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
2008 The U11-48K protein contacts the 5' splice site of U12-type introns and the U11-59K protein. Molecular and cellular biology 41 18347052
2024 MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons. Neuron 39 38697112
2019 MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity. Molecular & cellular proteomics : MCP 39 31839598
2022 In-Depth In Vivo Crosslinking in Minutes by a Compact, Membrane-Permeable, and Alkynyl-Enrichable Crosslinker. Analytical chemistry 38 35575683
2009 Solution structure of the U11-48K CHHC zinc-finger domain that specifically binds the 5' splice site of U12-type introns. Structure (London, England : 1993) 23 19217400
2024 Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome. Science (New York, N.Y.) 20 38484052
2018 Quantitative mapping of RNA-mediated nuclear estrogen receptor β interactome in human breast cancer cells. Scientific data 20 29509190
2021 Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins. Nucleic acids research 17 34133714
2021 Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model. Nutrition & metabolism 16 33691721
2019 SETD1A Methyltransferase Is Physically and Functionally Linked to the DNA Damage Repair Protein RAD18. Molecular & cellular proteomics : MCP 13 31076518
2022 SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members. Life science alliance 11 36375840
2022 TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells. Biochemical and biophysical research communications 9 35944360
2025 Structural basis of 5' splice site recognition by the minor spliceosome. Molecular cell 6 39809272
2022 Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer's disease. Life science alliance 6 35914814