Structural basis of rotavirus RNA chaperone displacement and RNA annealing.
Bravo, Jack P K
Gail, Emma H
Proceedings of the National Academy of Sciences of the United States of America
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Bravo, J. P. K., 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.. Proceedings of the National Academy of Sciences of the United States of America, 118 (41) https://doi.org/10.1073/pnas.2100198118
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.
Rotavirus, Ribonucleoproteins, Genome Assembly, Rna Chaperones
Biotechnology and Biological Sciences Research Council (BB/M011151/1, BB/M012573/1)
Wellcome Trust (094232, 208385/Z/17/Z, 213437/Z/18/Z, 108466/Z/15/Z, 220628/Z/20/Z)
External DOI: https://doi.org/10.1073/pnas.2100198118
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330417
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/