Biotechnology and Biological Sciences Research Council (BBSRC)
BB/M011151/1
United Kingdom
Citation
Journal: Proc Natl Acad Sci U S A / Year: 2021 Title: Structural basis of rotavirus RNA chaperone displacement and RNA annealing. Authors: Jack P K Bravo / Kira Bartnik / Luca Venditti / Julia Acker / Emma H Gail / Alice Colyer / Chen Davidovich / Don C Lamb / Roman Tuma / Antonio N Calabrese / Alexander Borodavka / 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 ...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.
History
Deposition
Aug 26, 2021
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Header (metadata) release
Sep 29, 2021
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Map release
Sep 29, 2021
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Update
Oct 20, 2021
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Current status
Oct 20, 2021
Processing site: PDBe / Status: Released
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