Bravo, JPK, Bartnik, K, Venditti, L et al. (8 more authors) (2021) Structural basis of rotavirus RNA chaperone displacement and RNA annealing. Proceedings of the National Academy of Sciences, 118 (41). e2100198118. ISSN 0027-8424
Abstract
Rotavirus genomes are distributed between 11 distinct RNA molecules, all of which must be selectively copackaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP2. Here, we report that NSP2 autoregulates its chaperone activity through its C-terminal region (CTR) that promotes RNA–RNA interactions by limiting its helix-unwinding activity. Unexpectedly, structural proteomics data revealed that the CTR does not directly interact with RNA, while accelerating RNA release from NSP2. Cryo–electron microscopy reconstructions of an NSP2–RNA complex reveal a highly conserved acidic patch on the CTR, which is poised toward the bound RNA. Virus replication was abrogated by charge-disrupting mutations within the acidic patch but completely restored by charge-preserving mutations. Mechanistic similarities between NSP2 and the unrelated bacterial RNA chaperone Hfq suggest that accelerating RNA dissociation while promoting intermolecular RNA interactions may be a widespread strategy of RNA chaperone recycling.
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Copyright, Publisher and Additional Information: | Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). | ||||
Keywords: | RNA chaperones; ribonucleoproteins; genome assembly; rotavirus | ||||
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Institution: | The University of Leeds | ||||
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Bioinformatics (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Biomolecular Mass Spectroscopy (Leeds) |
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Depositing User: | Symplectic Publications | ||||
Date Deposited: | 16 Aug 2021 09:42 | ||||
Last Modified: | 29 Mar 2022 15:01 | ||||
Status: | Published | ||||
Publisher: | National Academy of Sciences | ||||
Identification Number: | https://doi.org/10.1073/pnas.2100198118 |