A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure

Bonilla, Steve L.; Sherlock, Madeline E.; MacFadden, Andrea; Kieft, Jeffrey S.

doi:10.1126/science.abe8526

A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure

Journal Article · 19 November 2021 · Science

DOI:https://doi.org/10.1126/science.abe8526· OSTI ID:1982951

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Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; RNA BioScience Initiative, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo–electron microscopy (cryo-EM), we visualized the structure of the mysterious viral transfer RNA (tRNA)–like structure (TLS) from the brome mosaic virus, which affects replication, translation, and genome encapsidation. Structures in isolation and those bound to tyrosyl-tRNA synthetase (TyrRS) show that this ~55-kilodalton purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs substantially from that of tRNA. Our study reveals how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions, and we highlight the utility of cryo-EM for visualizing small, conformationally dynamic structured RNAs.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1982951

Journal Information:: Science, Vol. 374, Issue 6570; ISSN 0036-8075

Publisher:: AAAS

Country of Publication:: United States

Language:: English

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