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

Wan R, Bai R, Yan C, Lei J, Shi Y
Cell 177 339-351.e13 (2019)
Related entries: 6j6g, 6j6h, 6j6q

Cited: 40 times
EuropePMC logo PMID: 30879786

Abstract

Pre-mRNA splicing is executed by the spliceosome. Structural characterization of the catalytically activated complex (B∗) is pivotal for understanding the branching reaction. In this study, we assembled the B∗ complexes 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 small nuclear RNA (snRNA) and the branch point sequence (BPS) is discretely away from the 5'-splice site (5'SS) in the three 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, 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.

Reviews citing this publication (8)

  1. Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Rogalska ME, Vivori C, Valcárcel J. Nat Rev Genet 24 251-269 (2023)
  2. The SF3b complex: splicing and beyond. Sun C. Cell Mol Life Sci 77 3583-3595 (2020)
  3. Structural and functional modularity of the U2 snRNP in pre-mRNA splicing. van der Feltz C, Hoskins AA. Crit Rev Biochem Mol Biol 54 443-465 (2019)
  4. DEAH-Box RNA Helicases in Pre-mRNA Splicing. De Bortoli F, Espinosa S, Zhao R. Trends Biochem Sci 46 225-238 (2021)
  5. Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities. Blijlevens M, Li J, van Beusechem VW. Int J Mol Sci 22 5110 (2021)
  6. An RNA-centric historical narrative around the Protein Data Bank. Westhof E, Leontis NB. J Biol Chem 296 100555 (2021)
  7. Recent advances and current trends in cryo-electron microscopy. Guaita M, Watters SC, Loerch S. Curr Opin Struct Biol 77 102484 (2022)
  8. Zinc finger structure determination by NMR: Why zinc fingers can be a handful. Neuhaus D. Prog Nucl Magn Reson Spectrosc 130-131 62-105 (2022)

Articles citing this publication (32)



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