Bai Rui, Yuan Meng, Zhang Pu, Luo Ting, Shi Yigong, Wan Ruixue
Research Center for Industries of the Future, Key Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Xihu District, Hangzhou 310024, Zhejiang Province, China.
Westlake Laboratory of Life Sciences and Biomedicine, Xihu District, Hangzhou 310024, Zhejiang Province, China.
Science. 2024 Mar 15;383(6688):1245-1252. doi: 10.1126/science.adn7272. Epub 2024 Mar 14.
The minor spliceosome, which is responsible for the splicing of U12-type introns, comprises five small nuclear RNAs (snRNAs), of which only one is shared with the major spliceosome. In this work, we report the 3.3-angstrom cryo-electron microscopy structure of the fully assembled human minor spliceosome pre-B complex. The atomic model includes U11 small nuclear ribonucleoprotein (snRNP), U12 snRNP, and U4atac/U6atac.U5 tri-snRNP. U11 snRNA is recognized by five U11-specific proteins (20K, 25K, 35K, 48K, and 59K) and the heptameric Sm ring. The 3' half of the 5'-splice site forms a duplex with U11 snRNA; the 5' half is recognized by U11-35K, U11-48K, and U11 snRNA. Two proteins, CENATAC and DIM2/TXNL4B, specifically associate with the minor tri-snRNP. A structural analysis uncovered how two conformationally similar tri-snRNPs are differentiated by the minor and major prespliceosomes for assembly.
负责U12型内含子剪接的次要剪接体由五种小核RNA（snRNA）组成，其中只有一种与主要剪接体重叠。在这项研究中，我们报道了完全组装的人类次要剪接体pre-B复合物的3.3埃冷冻电镜结构。原子模型包括U11小核核糖核蛋白（snRNP）、U12 snRNP和U4atac/U6atac.U5三snRNP。U11 snRNA被五种U11特异性蛋白（20K、25K、35K、48K和59K）和七聚体Sm环识别。5'剪接位点的3'半段与U11 snRNA形成双链体；5'半段被U11-35K、U11-48K和U11 snRNA识别。两种蛋白CENATAC和DIM2/TXNL4B特异性地与次要三snRNP结合。结构分析揭示了两种构象相似的三snRNP如何被次要和主要剪接前体区分用于组装。
