Biotechnology and Biological Sciences Research Council (BBSRC)
BB/M011151/1
英国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2021 タイトル: Structural basis of rotavirus RNA chaperone displacement and RNA annealing. 著者: 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 / 要旨: 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.
U: Non-structural protein 2 A: Non-structural protein 2 B: Non-structural protein 2 C: Non-structural protein 2 D: Non-structural protein 2 E: Non-structural protein 2 F: Non-structural protein 2 G: Non-structural protein 2