A unique mechanism of snRNP core assembly

Yingzhi Wang, Xiaoshuang Chen, Xi Kong, Yunfeng Chen, Zixi Xiang, Yue Xiang, Yan Hu, Yan Hou, Shijie Zhou, Congcong Shen, Li Mu, Dan Su and Rundong Zhang ()
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Yingzhi Wang: Sichuan University
Xiaoshuang Chen: Sichuan University
Xi Kong: Sichuan University
Yunfeng Chen: Sichuan University
Zixi Xiang: Sichuan University
Yue Xiang: Sichuan University
Yan Hu: Sichuan University
Yan Hou: Sichuan University
Shijie Zhou: Sichuan University
Congcong Shen: Sichuan University
Li Mu: Sichuan University
Dan Su: Sichuan University
Rundong Zhang: Sichuan University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58461-7

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