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Cited by 7RNA Research and SplicingRNA and protein synthesis mechanismsNuclear Structure and Function

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A unique mechanism of snRNP core assembly

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Wang, Yingzhi, Chen, Xiaoshuang, Kong, Xi, Chen, Yunfeng, Xiang, Zixi, Xiang, Yue, Hu, Yan, Hou, Yan, Zhou, Shijie, Shen, Congcong, Mu, Li, Su, Dan, Zhang, Rundong·2025·Nature Communications
DOI 10.1038/s41467-025-58461-7PMC PMC11965559

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Abstract

ABSTRACT The assembly of spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around each snRNA and typically requires several essential assembly chaperones, particularly the SMN-Gemins complex implicated in spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. To unravel this enigma, we systematically investigated snRNP core assembly in budding yeast using biochemical and genetic approaches. We discovered two distinct pathways in budding yeast: chaperone-mediated and direct. The chaperone-mediated pathway involves two proteins, Brr1 and a novel protein, Lot5, but is inefficient. Lot5 binds D1/D2/F/E/G to form a heterohexameric ring (6S). Brr1 binds D1/D2/F/E/G and 6S but cannot displace Lot5 to facilitate assembly. Disruption of both BRR1 and LOT5 genes caused mild growth retardation, but LOT5 overexpression substantially impeded growth. The direct pathway uniquely involves F/E/G as a trimer and a stable D1/D2/F/E/G intermediate complex, explaining the non-essentiality of assembly chaperones. These findings unveil a unique assembly mechanism of snRNP cores, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.

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Metadata

Authors
Wang, Y., Chen, X., Kong, X., Chen, Y., Xiang, Z., Xiang, Y., Hu, Y., Hou, Y., Zhou, S., Shen, C., Mu, L., Su, D., & Zhang, R.
Affiliations
Sichuan University (CN)
Corresponding author
Zhang, Rundong
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-04-02
Volume
16
Issue
1
Pages
3166-3166
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-58461-7
PMC
PMC11965559
OpenAlex
W4409148881
Cited by
7
References
3
Citations by year
2026: 4 · 2025: 3
FWCI
2.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Science and Technology of the People's Republic of China (2017YFA0504300, 2017YFA0505900)
  • Department of Science and Technology of Sichuan Province (2020YJ0209)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
Sm proteins, SMN complex, spinal muscular atrophy, spliceosome, Saccharomyces cerevisiae, assembly intermediates
MeSH terms
Protein Binding, RNA, Small Nuclear, Saccharomyces cerevisiae, Spliceosomes, Molecular Chaperones, Saccharomyces cerevisiae Proteins, snRNP Core Proteins, SMN Complex Proteins

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