Open AccessStructural basis of rotavirus RNA chaperone displacement and RNA annealing
Author(s) -
Jack P. K. Bravo,
Kira Bartnik,
Luca Venditti,
Julia Acker,
Emma H Gail,
Alice Colyer,
Chen Davidovich,
Don C. Lamb,
Roman Tůma,
Antonio N. Calabrese,
Alexander Borodavka
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100198118
Subject(s) - rna , biology , non coding rna , rna dependent rna polymerase , rna editing , microbiology and biotechnology , chaperone (clinical) , genetics , computational biology , gene , medicine , pathology
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.