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小核核糖核蛋白核心组装的独特机制。

A unique mechanism of snRNP core assembly.

作者信息

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

机构信息

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, P R China.

State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, P R China.

出版信息

Nat Commun. 2025 Apr 2;16(1):3166. doi: 10.1038/s41467-025-58461-7.

DOI:10.1038/s41467-025-58461-7
PMID:40175367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11965559/
Abstract

The assembly of most spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around snRNA, typically requiring essential assembly chaperones like the SMN complex, associated with spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. Here, we reveal two distinct pathways in budding yeast: an inefficient chaperone-mediated pathway involving Brr1 and a novel factor, Lot5, and a direct pathway. 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 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 chaperones. These findings unveil a unique snRNP core assembly mechanism, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.

摘要

大多数剪接体snRNP核心的组装涉及七种Sm蛋白（D1/D2/F/E/G/D3/B）围绕snRNA形成一个环，通常需要诸如与脊髓性肌萎缩症（SMA）相关的SMN复合物等必需的组装伴侣蛋白。引人注目的是，在芽殖酵母中，snRNP核心组装仅涉及Brr1，它是Gemin2的非必需同源物。在这里，我们揭示了芽殖酵母中的两条不同途径：一条效率低下的由伴侣蛋白介导的途径，涉及Brr1和一个新因子Lot5，以及一条直接途径。Lot5与D1/D2/F/E/G结合形成一个异源六聚体环（6S）。Brr1与D1/D2/F/E/G和6S结合，但不能取代Lot5来促进组装。BRR1和LOT5基因的破坏导致轻微的生长迟缓，但Lot5的过表达严重阻碍生长。直接途径独特地涉及F/E/G作为三聚体和一个稳定的D1/D2/F/E/G中间复合物，这解释了伴侣蛋白的非必需性。这些发现揭示了一种独特的snRNP核心组装机制，阐明了组装伴侣蛋白的进化，并为研究SMA病理生理学提供了途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/66966772e0ff/41467_2025_58461_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/77dba64abd39/41467_2025_58461_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/61887a0a0ae2/41467_2025_58461_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/d19ae3113e5f/41467_2025_58461_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/d6af622d1815/41467_2025_58461_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/3564b79ce7df/41467_2025_58461_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/1657ef466636/41467_2025_58461_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/4c1bc2d48473/41467_2025_58461_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/0506199d4315/41467_2025_58461_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/66966772e0ff/41467_2025_58461_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/77dba64abd39/41467_2025_58461_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/61887a0a0ae2/41467_2025_58461_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/d19ae3113e5f/41467_2025_58461_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/d6af622d1815/41467_2025_58461_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/3564b79ce7df/41467_2025_58461_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/1657ef466636/41467_2025_58461_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/4c1bc2d48473/41467_2025_58461_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/0506199d4315/41467_2025_58461_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38f/11965559/66966772e0ff/41467_2025_58461_Fig9_HTML.jpg

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3
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