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Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching

Ruixue Wan, Rui Bai, Chuangye Yan, Jianlin Lei, Yigong Shi
doi: https://doi.org/10.1101/500363
Ruixue Wan
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
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Rui Bai
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
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Chuangye Yan
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
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Jianlin Lei
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaTechnology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Yigong Shi
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, ChinaInstitute of Biology, Westlake Institute for Advanced Study; School of Life Sciences, Westlake University, 18 Shilongshan Road, Xihu District, Hangzhou 310024, Zhejiang Province, China
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Summary

Pre-mRNA splicing is executed by the spliceosome. Structural characterization of the catalytically activated complex (B*) is pivotal for mechanistic understanding of catalysis of the branching reaction by the spliceosome. In this study, we assembled the B* complex on two different pre-mRNAs from Saccharomyces cerevisiae and determined the cryo-EM structures of four distinct B complexes at overall resolutions of 2.9-3.8 Å. The duplex between U2 snRNA and the branch point sequence (BPS) is located 13-20 Å away from the 5’-splice site (5’SS) in the B* complexes that are devoid of the step I splicing factors Yju2 and Cwc25. Recruitment of Yju2 into the active site brings the U2/BPS duplex into the vicinity of 5’SS, ready for branching. In the absence of Cwc25, the nucleophile from BPS is positioned about 4 Å away from, and remains to be activated by, the catalytic metal M2. This analysis reveals the functional mechanism of Yju2 and Cwc25 in branching. These four structures constitute compelling evidence for substrate-specific conformations of the spliceosome in a major functional state.

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Posted December 19, 2018.
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Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching
Ruixue Wan, Rui Bai, Chuangye Yan, Jianlin Lei, Yigong Shi
bioRxiv 500363; doi: https://doi.org/10.1101/500363
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Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching
Ruixue Wan, Rui Bai, Chuangye Yan, Jianlin Lei, Yigong Shi
bioRxiv 500363; doi: https://doi.org/10.1101/500363

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