Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching.
basic_science · Level V
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- Record sourced from PubMed, PMID 30879786.
- Also identified by DOI 10.1016/j.cell.2019.02.006.
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Abstract
Pre-mRNA splicing is executed by the spliceosome. Structural characterization of the catalytically activated complex (B<sup>∗</sup>) is pivotal for understanding the branching reaction. In this study, we assembled the B<sup>∗</sup> complexes on two different pre-mRNAs from Saccharomyces cerevisiae and determined the cryo-EM structures of four distinct B<sup>∗</sup> complexes at overall resolutions of 2.9-3.8 Å. The duplex between U2 small nuclear RNA (snRNA) and the branch point sequence (BPS) is discretely away from the 5'-splice site (5'SS) in the three B<sup>∗</sup> 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, with the BPS nucleophile positioned 4 Å away from the catalytic metal M2. This analysis reveals the functional mechanism of Yju2 and Cwc25 in branching. These structures on different pre-mRNAs reveal substrate-specific conformations of the spliceosome in a major functional state.
Medical subject headings
- Spliceosomes