Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome.

Bhatt, Pramod R; Scaiola, Alain; Loughran, Gary; Leibundgut, Marc; Kratzel, Annika; Meurs, Romane; Dreos, René; O'Connor, Kate M; McMillan, Angus; Bode, Jeffrey W; Thiel, Volker; Gatfield, David; Atkins, John F; Ban, Nenad (2021). Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome. Science, 372(6548), pp. 1306-1313. American Association for the Advancement of Science 10.1126/science.abf3546

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Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo-electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot structure that lodges at the entry to the ribosomal messenger RNA (mRNA) channel to generate tension in the mRNA and promote frameshifting, whereas the nascent viral polyprotein forms distinct interactions with the ribosomal tunnel. Biochemical experiments validate the structural observations and reveal mechanistic and regulatory features that influence frameshifting efficiency. Finally, we compare compounds previously shown to reduce frameshifting with respect to their ability to inhibit SARS-CoV-2 replication, establishing coronavirus frameshifting as a target for antiviral intervention.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kratzel, Annika and Thiel, Volker Earl

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0036-8075

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

05 Aug 2021 09:14

Last Modified:

05 Aug 2021 09:14

Publisher DOI:

10.1126/science.abf3546

PubMed ID:

34029205

BORIS DOI:

10.48350/157744

URI:

https://boris.unibe.ch/id/eprint/157744

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