Structural basis of rotavirus RNA chaperone displacement and RNA annealing.

Change log
Bravo, Jack P K 
Venditti, Luca 
Gail, Emma H 

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
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Conference Name
Journal ISSN
Volume Title
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)