Snapshots of the first-step self-splicing of Tetrahymena ribozyme revealed by cryo-EM.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
22 02 2023
Historique:
accepted: 18 01 2023
revised: 20 12 2022
received: 01 07 2022
pubmed: 21 1 2023
medline: 25 2 2023
entrez: 20 1 2023
Statut: ppublish

Résumé

Tetrahymena ribozyme is a group I intron, whose self-splicing is the result of two sequential ester-transfer reactions. To understand how it facilitates catalysis in the first self-splicing reaction, we used cryogenic electron microscopy (cryo-EM) to resolve the structures of L-16 Tetrahymena ribozyme complexed with a 11-nucleotide 5'-splice site analog substrate. Four conformations were achieved to 4.14, 3.18, 3.09 and 2.98 Å resolutions, respectively, corresponding to different splicing intermediates during the first enzymatic reaction. Comparison of these structures reveals structural alterations, including large conformational changes in IGS/IGSext (P1-P1ext duplex) and J5/4, as well as subtle local rearrangements in the G-binding site. These structural changes are required for the enzymatic activity of the Tetrahymena ribozyme. Our study demonstrates the ability of cryo-EM to capture dynamic RNA structural changes, ushering in a new era in the analysis of RNA structure-function by cryo-EM.

Identifiants

pubmed: 36660826
pii: 6993854
doi: 10.1093/nar/gkac1268
pmc: PMC9943679
doi:

Substances chimiques

RNA 63231-63-0
RNA, Catalytic 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1317-1325

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Xiaojing Zhang (X)

Department of Urology, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

Shanshan Li (S)

Department of Urology, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

Grigore Pintilie (G)

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

Michael Z Palo (MZ)

Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.

Kaiming Zhang (K)

Department of Urology, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

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Classifications MeSH