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Structure of a pre-catalytic spliceosome

Author

Listed:
  • Clemens Plaschka

    (MRC Laboratory of Molecular Biology)

  • Pei-Chun Lin

    (MRC Laboratory of Molecular Biology)

  • Kiyoshi Nagai

    (MRC Laboratory of Molecular Biology)

Abstract

Intron removal requires assembly of the spliceosome on precursor mRNA (pre-mRNA) and extensive remodelling to form the spliceosome’s catalytic centre. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution. The mobile U2 small nuclear ribonucleoprotein particle (snRNP) associates with U4/U6.U5 tri-snRNP through the U2/U6 helix II and an interface between U4/U6 di-snRNP and the U2 snRNP SF3b-containing domain, which also transiently contacts the helicase Brr2. The 3′ region of the U2 snRNP is flexibly attached to the SF3b-containing domain and protrudes over the concave surface of tri-snRNP, where the U1 snRNP may reside before its release from the pre-mRNA 5′ splice site. The U6 ACAGAGA sequence forms a hairpin that weakly tethers the 5′ splice site. The B complex proteins Prp38, Snu23 and Spp381 bind the Prp8 N-terminal domain and stabilize U6 ACAGAGA stem–pre-mRNA and Brr2–U4 small nuclear RNA interactions. These results provide important insights into the events leading to active site formation.

Suggested Citation

  • Clemens Plaschka & Pei-Chun Lin & Kiyoshi Nagai, 2017. "Structure of a pre-catalytic spliceosome," Nature, Nature, vol. 546(7660), pages 617-621, June.
  • Handle: RePEc:nat:nature:v:546:y:2017:i:7660:d:10.1038_nature22799
    DOI: 10.1038/nature22799
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    Cited by:

    1. Josef Pánek & Adriana Roithová & Nenad Radivojević & Michal Sýkora & Archana Bairavasundaram Prusty & Nicholas Huston & Han Wan & Anna Marie Pyle & Utz Fischer & David Staněk, 2023. "The SMN complex drives structural changes in human snRNAs to enable snRNP assembly," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. D. Herreros & R. R. Lederman & J. M. Krieger & A. Jiménez-Moreno & M. Martínez & D. Myška & D. Strelak & J. Filipovic & C. O. S. Sorzano & J. M. Carazo, 2023. "Estimating conformational landscapes from Cryo-EM particles by 3D Zernike polynomials," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Xiechao Zhan & Yichen Lu & Yigong Shi, 2024. "Molecular basis for the activation of human spliceosome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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