Structural basis of rotavirus RNA chaperone displacement and RNA annealing.
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Authors
Bravo, Jack PK
Venditti, Luca
Gail, Emma H
Tuma, Roman
Publication Date
2021-10-12Journal Title
Proc Natl Acad Sci U S A
ISSN
0027-8424
Publisher
Proceedings of the National Academy of Sciences
Volume
118
Issue
41
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Bravo, J. P., Bartnik, K., Venditti, L., Acker, J., Gail, E. H., Colyer, A., Davidovich, C., et al. (2021). Structural basis of rotavirus RNA chaperone displacement and RNA annealing.. Proc Natl Acad Sci U S A, 118 (41) https://doi.org/10.1073/pnas.2100198118
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.
Identifiers
External DOI: https://doi.org/10.1073/pnas.2100198118
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329648
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