Affinage

SNU13

NHP2-like protein 1 · UniProt P55769

Round 2 corrected
Length
128 aa
Mass
14.2 kDa
Annotated
2026-04-28
64 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNU13 (15.5K in human, Snu13p in yeast) is a K-turn RNA-binding protein that serves as the nucleation factor for the hierarchical assembly of three distinct RNP complexes: the spliceosomal U4/U6 snRNP, box C/D snoRNPs, and the U3 snoRNP box B/C complex (PMID:11081632, PMID:12417735, PMID:12381732). It recognizes K-turn motifs in its target RNAs through an induced-fit mechanism that stabilizes the kinked RNA backbone, and it presents distinct protein-protein contact surfaces to recruit complex-specific partners such as NOP56, NOP58, fibrillarin, and hPrp31 for snoRNPs and U4/U6, respectively (PMID:16782898, PMID:15659359). Its interaction with the assembly factor Rsa1p/NUFIP, mediated by an electrostatic interface centered on E72/D73 of Snu13p, is mutually exclusive with mature snoRNP protein contacts and prevents premature snoRNP activation (PMID:24234454). The three-dimensional fold of SNU13 is deeply conserved from red algae to humans, and the Snu13–U4 snRNA interface has been shown to be pharmacologically targetable (PMID:26833716).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2000 High

    The discovery that Snu13p/15.5K binds both U4 snRNA and box C/D snoRNAs via a shared stem-internal loop-stem motif established SNU13 as a dual-function RNP core protein bridging splicing and rRNA modification machineries.

    Evidence In vitro binding assays, mass spectrometry of U4/U6.U5 tri-snRNP, yeast genetic depletion with RNA metabolism phenotype

    PMID:11081632

    Open questions at the time
    • Mechanism of 15.5K recruitment to RNA not yet defined at atomic level
    • Whether 15.5K binding alone is sufficient for downstream protein assembly unknown
  2. 2002 High

    Reconstitution experiments demonstrated that 15.5K binding is the obligate first step in hierarchical box C/D snoRNP assembly and also nucleates U3 snoRNP box B/C complex formation, revealing a general organizational principle for K-turn-containing RNPs.

    Evidence In vitro RNP assembly on U14 snoRNA with sequential protein addition; UV cross-linking and assembly assays on U3 snoRNA box B/C motif in vitro; HeLa cell microinjection for nucleolar localization

    PMID:12381732 PMID:12417735

    Open questions at the time
    • Whether 15.5K contacts downstream snoRNP proteins directly or only via RNA-mediated conformational changes was unresolved
    • Stoichiometry of 15.5K binding on U3 snoRNA (two K-turns) not fully characterized
  3. 2003 High

    Detailed analysis of the two K-turn motifs in U3 snoRNA showed that Snu13p binds both independently with different affinities, and that both binding events are required for U3 snoRNP function, establishing that multi-site K-turn recognition is functionally essential.

    Evidence Chemical probing of reconstituted complexes, gel-shift assays, phylogenetic analysis, yeast U3 mutant functional assays

    PMID:12810916

    Open questions at the time
    • Structural basis for differential affinity of the two K-turns not resolved
    • Whether simultaneous occupancy of both sites by Snu13p is required in vivo unknown
  4. 2005 Medium

    Molecular dynamics and chemical probing revealed that 15.5K folds the K-turn RNA through an induced-fit mechanism, resolving the question of whether the RNA is pre-folded or actively structured by the protein.

    Evidence Molecular dynamics simulation of free and bound U4 5' stem-loop, chemical modification experiments

    PMID:15659359

    Open questions at the time
    • Induced-fit conclusion based on computational simulation with limited experimental benchmarks
    • Whether the same induced-fit mechanism applies to box C/D K-turns not tested
  5. 2006 High

    Systematic surface mutagenesis of 15.5K demonstrated that it uses distinct protein surfaces to nucleate each of its three RNP complexes and that direct protein-protein contacts (not only RNA-mediated effects) are essential, explaining how one protein can serve as a platform for divergent assemblies.

    Evidence Surface mutagenesis of 15.5K tested in U4/U6, box C/D snoRNP, and U3 box B/C in vitro assembly assays; direct 15.5K–hU3-55K interaction assay

    PMID:16782898

    Open questions at the time
    • Atomic-resolution structures of complete ternary complexes lacking
    • Whether surface utilization changes in the context of fully assembled particles unknown
  6. 2007 Medium

    The solution NMR structure of free 15.5K identified conformational flexibility in the alpha3 helix, suggesting a structural basis for adaptability in K-turn recognition.

    Evidence Solution NMR structure, 15N relaxation, H/D exchange on free human 15.5K protein

    PMID:18044964

    Open questions at the time
    • No corresponding NMR structure of the RNA-bound form for direct comparison
    • Functional relevance of alpha3 flexibility not validated by mutagenesis
  7. 2013 High

    Structural and genetic characterization of the Snu13p–Rsa1p/NUFIP interface revealed a regulated assembly checkpoint: the Rsa1p binding surface on Snu13p overlaps with mature snoRNP protein contacts, preventing premature snoRNP activation until assembly factor release.

    Evidence NMR structure and molecular docking of Snu13p–Rsa1p complex, electrostatic interface mutagenesis, yeast growth and snoRNP formation assays

    PMID:24234454

    Open questions at the time
    • Trigger for Rsa1p/NUFIP release during maturation not identified
    • Whether this checkpoint operates identically for all box C/D snoRNPs unknown
  8. 2019 Medium

    NMR of the free U14 K-turn motif showed it adopts a pre-folded conformation even without Snu13p or divalent ions, partially revising the earlier induced-fit model by showing that some C/D box K-turns are intrinsically structured before protein binding.

    Evidence Solution NMR of free kt-U14 RNA, NMR-monitored Snu13p binding

    PMID:30914254

    Open questions at the time
    • Generalizability to other C/D box K-turns not tested
    • Quantitative comparison of pre-folding extent across different K-turn substrates lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the precise trigger for Rsa1p/NUFIP release during snoRNP maturation, whether the induced-fit versus pre-folded K-turn distinction has functional consequences for assembly kinetics in vivo, and whether pharmacological disruption of the Snu13–K-turn interface can be achieved with cellular activity.
  • No in vivo kinetic measurements of snoRNP assembly steps
  • No cell-active small molecule inhibitors of Snu13–RNA interaction reported in peer-reviewed literature
  • Full cryo-EM or crystal structures of complete human box C/D snoRNP with 15.5K in native context not described in this timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0005198 structural molecule activity 3
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 6
Partners
FBLNOP56NOP58NUFIP1PRPF31U3-55K
Complex memberships
U3 snoRNPU4/U6 snRNPbox C/D snoRNP

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Snu13p (yeast)/15.5K (human) was identified as a component of the U4/U6.U5 tri-snRNP that also associates with box C/D snoRNAs. The box C/D motif can be folded into a stem-internal loop-stem structure almost identical to the 15.5K binding site in U4 snRNA, and binds Snu13p/15.5K in vitro. Genetic depletion of Snu13p in yeast causes a major defect in RNA metabolism, establishing a shared core RNP structure between box C/D snoRNPs and the spliceosomal U4 snRNP. In vitro binding assay, yeast genetic depletion, structural RNA analysis, mass spectrometry Cell High 11081632
2002 15.5K (SNU13) binding to the box C/D motif is essential for the hierarchical assembly of the remaining snoRNP proteins (NOP56, NOP58, fibrillarin, TIP48, TIP49) onto U14 snoRNA in vitro. The conserved stem II sequence of the box C/D motif (absent in U4 5' stem-loop) determines binding specificity of NOP56, NOP58, and fibrillarin, and is essential for nucleolar localization of U14 snoRNA in HeLa cells. In vitro RNP assembly assay, HeLa cell microinjection, mutational analysis of RNA elements Molecular and cellular biology High 12417735
2002 The association of hU3-55K with the U3 snoRNA box B/C motif is dependent on prior binding of 15.5K to the box B/C motif, as well as on a conserved flanking RNA structure. hU3-55K directly cross-links to the U3BC RNA, and the box B/C motif adopts a K-turn-like structure similar to the U4 5' stem-loop and box C/D motif. In vitro assembly assay, UV cross-linking, RNA structural analysis The Journal of biological chemistry High 12381732
2003 The 15.5K/Snu13p protein binds independently to both the C'/D and B/C motifs of U3 snoRNA. The B/C motif has a higher affinity for Snu13p than the C'/D motif despite having a highly reduced stem I (1 bp). Conservation of residues 2 and 3 in the B/C K-turn bulge is more important for Snu13p binding and U3 snoRNA function than corresponding residues in the C'/D K-turn, demonstrating that binding of 15.5K/Snu13p to both motifs is essential for U3 snoRNP assembly and activity. Chemical probing of in vitro reconstituted RNA/protein complexes, gel-shift assays, phylogenetic analysis, yeast functional assays with mutant U3 snoRNA RNA (New York, N.Y.) High 12810916
2005 The 15.5K protein folds its cognate K-turn RNA through an induced-fit mechanism: the free U4 snRNA 5' stem-loop lacks stable secondary structure and undergoes conformational fluctuations (loss of G-A base pairs, opening of the K-turn) that are suppressed upon 15.5K binding. Protein binding stabilizes specific RNA conformational states including canonical G-C base pairs and the kinked RNA backbone. Molecular dynamics simulation, chemical RNA modification experiments (biochemical probing of free vs. protein-bound RNA) RNA (New York, N.Y.) Medium 15659359
2006 15.5K mediates assembly of the U4/U6 snRNP, box C/D snoRNP, and U3 box B/C RNP through both RNA-induced conformational changes and direct protein-protein contacts. Surface mutagenesis of 15.5K demonstrated that each of the three distinct RNP complexes requires a distinct set of surface regions on 15.5K for assembly. Direct protein-protein interaction between 15.5K and hU3-55K was demonstrated, confirming that protein-protein contacts are essential alongside RNA-mediated interactions. Surface mutagenesis of 15.5K, in vitro RNP assembly assays, direct protein-protein interaction assay Molecular and cellular biology High 16782898
2007 The solution NMR structure of free 15.5K (SNU13) shows a well-structured protein with conformational flexibility primarily in the alpha3 helix. 15N NMR relaxation and H/D exchange experiments reveal fast time-scale motions and limited intermediate/slow motions, suggesting that local flexibility in alpha3 contributes to K-turn RNA recognition and binding. Solution NMR structure determination, 15N NMR relaxation, H/D exchange Biochemistry Medium 18044964
2013 Snu13p/15.5K directly interacts with the assembly factor Rsa1p/NUFIP. NMR structure determination and docking identified a specific interface where residues R249, R246, K250 in Rsa1p and E72, D73 in Snu13p form electrostatic interactions shielded by hydrophobic residues, with W253 of Rsa1p inserted into a hydrophobic cavity of Snu13p. This interaction is mutually exclusive with active snoRNP protein interactions (based on archaeal sRNP structural templates). Individual mutations in yeast impair both cell growth and snoRNP formation, demonstrating that Rsa1p/NUFIP prevents premature activity of pre-snoRNPs. NMR structure determination, molecular docking, biophysical assays, yeast mutagenesis with growth and snoRNP formation readouts, imaging Nucleic acids research High 24234454
2016 X-ray crystallographic analysis of Snu13 from the minimalist spliceosome of Cyanidioschyzon merolae (CmSnu13) revealed near-identical three-dimensional structure to yeast and human Snu13, demonstrating that Snu13 structure is deeply conserved. Evidence for conservation of Snu13 function in the C. merolae splicing pathway was also presented. X-ray crystallography Protein science Medium 26833716
2019 The free yeast U14 C/D box snoRNA K-turn motif (kt-U14) adopts a pre-folded conformation similar to the protein-bound K-turn even in the absence of divalent ions, displaying weak hydrogen bonds in U•U and G•A tandem base pairs. Snu13p binding stabilizes and rigidifies this conformation, establishing kt-U14 as the first reference example for canonical C/D box snoRNA K-turn motifs. Solution NMR structure determination of free RNA, protein-binding NMR experiments Biochimie Medium 30914254
2025 Small molecule ligands that bind the K-turn region of the yeast U4 snRNA were identified and one analog (compound 22) inhibits the binding of U4 snRNA to Snu13 in biochemical assays with an IC50 of 3.2 ± 0.4 µM, demonstrating that the Snu13–U4 snRNA interaction can be pharmacologically disrupted. Small molecule microarray screening, biophysical binding assays, deltaSHAPE RNA structure probing, MD simulations, biochemical inhibition assay bioRxivpreprint Medium bio_10.1101_2025.10.10.681657

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
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
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
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1999 The DNA sequence of human chromosome 22. Nature 808 10591208
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
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
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
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
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
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
2000 A common core RNP structure shared between the small nucleoar box C/D RNPs and the spliceosomal U4 snRNP. Cell 295 11081632
2002 Conserved stem II of the box C/D motif is essential for nucleolar localization and is required, along with the 15.5K protein, for the hierarchical assembly of the box C/D snoRNP. Molecular and cellular biology 173 12417735
1987 Involvement of fertilization antigen (FA-1) in involuntary immunoinfertility in humans. The Journal of clinical investigation 78 3316276
1988 Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid; preliminary observations in fetal and maternal tissues. European journal of obstetrics, gynecology, and reproductive biology 75 3224746
2003 A structural, phylogenetic, and functional study of 15.5-kD/Snu13 protein binding on U3 small nucleolar RNA. RNA (New York, N.Y.) 58 12810916
1994 Molecular identities of human sperm proteins that bind human zona pellucida: nature of sperm-zona interaction, tyrosine kinase activity, and involvement of FA-1. Molecular reproduction and development 50 7534465
2004 Characterization of the arginine deiminase operon of Streptococcus rattus FA-1. Applied and environmental microbiology 44 15006749
1989 Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid: localisation in the fetus and adult female genital tract. European journal of obstetrics, gynecology, and reproductive biology 43 2469607
2006 Protein-protein and protein-RNA contacts both contribute to the 15.5K-mediated assembly of the U4/U6 snRNP and the box C/D snoRNPs. Molecular and cellular biology 41 16782898
2017 CsI Pre-Intercalation in the Inorganic Framework for Efficient and Stable FA1-x Csx PbI3 (Cl) Perovskite Solar Cells. Small (Weinheim an der Bergstrasse, Germany) 39 28464500
1987 The fertilization antigen (FA-1) causes a reduction of fertility in actively immunized female rabbits. Journal of reproductive immunology 39 3625608
2002 The hU3-55K protein requires 15.5K binding to the box B/C motif as well as flanking RNA elements for its association with the U3 small nucleolar RNA in Vitro. The Journal of biological chemistry 38 12381732
2005 The snRNP 15.5K protein folds its cognate K-turn RNA: a combined theoretical and biochemical study. RNA (New York, N.Y.) 37 15659359
2013 Characterization of the interaction between protein Snu13p/15.5K and the Rsa1p/NUFIP factor and demonstration of its functional importance for snoRNP assembly. Nucleic acids research 33 24234454
1989 The detection in human sera of antisperm antibodies reactive with FA-1, an evolutionarily conserved antigen, and with murine spermatozoa. Fertility and sterility 31 2673845
1991 Human spermatozoal FA-1 binds with ZP3 of porcine zona pellucida. Journal of reproductive immunology 29 1875328
1990 Isolation, characterization, and inhibition kinetics of enolase from Streptococcus rattus FA-1. Infection and immunity 29 2318530
1995 Fertilization antigen (FA-1) completely blocks human sperm binding to human zona pellucida: FA-1 antigen may be a sperm receptor for zona pellucida in humans. Journal of reproductive immunology 28 8531189
1990 Antibodies to sperm surface fertilization antigen (FA-1): their specificities and site of interaction with sperm in male genital tract. Molecular reproduction and development 28 2372399
1994 Monoclonal antibody to human fertilization antigen-1 (FA-1) inhibits bovine fertilization in vitro: application in immunocontraception. Biology of reproduction 25 7918868
2002 Molecular cloning and sequencing of cDNA encoding for human FA-1 antigen. Molecular reproduction and development 23 12203836
2006 Effect of fertilization antigen (FA-1) DNA vaccine on fertility of female mice. Molecular reproduction and development 22 16894551
1976 Unbalanced growth and macromolecular synthesis in Streptococcus mutans FA-1. Infection and immunity 18 1270138
1994 Antibodies to sperm-specific human FA-1 inhibit in vitro fertilization in rhesus monkeys: development of a simian model for testing of anti-FA-1 contraceptive vaccine. Journal of reproductive immunology 17 7884740
2018 A Novel Compound, "FA-1" Isolated from Prunus mume, Protects Human Bronchial Epithelial Cells and Keratinocytes from Cigarette Smoke Extract-Induced Damage. Scientific reports 14 30065307
2017 Fabrication of CsxFA1-xPbI3 Mixed-Cation Perovskites via Gas-Phase-Assisted Compositional Modulation for Efficient and Stable Photovoltaic Devices. ACS applied materials & interfaces 14 29155561
2019 The yeast C/D box snoRNA U14 adopts a "weak" K-turn like conformation recognized by the Snu13 core protein in solution. Biochimie 11 30914254
2016 Conserved structure of Snu13 from the highly reduced spliceosome of Cyanidioschyzon merolae. Protein science : a publication of the Protein Society 9 26833716
2007 Functional implications for a prototypical K-turn binding protein from structural and dynamical studies of 15.5K. Biochemistry 6 18044964
1995 Thymosin alpha-1 and FA-1 monoclonal antibody affect fertilizing capacity of human sperm by modulating protein phosphorylation pattern. Journal of reproductive immunology 6 8531188
2022 Numerical Simulation and Optimization of Highly Stable and Efficient Lead-Free Perovskite FA1-xCsxSnI3-Based Solar Cells Using SCAPS. Materials (Basel, Switzerland) 5 35888227
1995 Thymosin alpha-1 and FA-1 monoclonal antibody affect murine preimplantation embryo development by modulating protein phosphorylation. Journal of reproductive immunology 5 8636928
1990 Interactions of micromolar concentrations of fluoride with Streptococcus rattus FA-1. Caries research 4 2364404
2025 In Situ Dual-Ionic Charge Compensation for CsxFA1-xPbI3 Perovskite Quantum Dot Solar Cells with Over 18% Efficiency. Advanced materials (Deerfield Beach, Fla.) 2 40534396
2021 Bandgap adjustment assisted preparation of >18% Cs FA1- PbI Br3- -based perovskite solar cells using a hybrid spraying process. RSC advances 2 35480162