Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome.
Science
; 372(6548): 1306-1313, 2021 06 18.
Article
in English
| MEDLINE | ID: covidwho-1228853
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Ribosomes
/
Viral Proteins
/
RNA, Viral
/
Frameshifting, Ribosomal
/
SARS-CoV-2
Type of study:
Observational study
/
Prognostic study
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
Affiliation country:
Science.abf3546
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