Clinically observed deletions in SARS-CoV-2 Nsp1 affect its stability and ability to inhibit translation.
FEBS Lett
; 596(9): 1203-1213, 2022 05.
Article
in English
| MEDLINE | ID: covidwho-1798052
ABSTRACT
Nonstructural protein 1 (Nsp1) of SARS-CoV-2 inhibits host cell translation through an interaction between its C-terminal domain and the 40S ribosome. The N-terminal domain (NTD) of Nsp1 is a target of recurring deletions, some of which are associated with altered COVID-19 disease progression. Here, we characterize the efficiency of translational inhibition by clinically observed Nsp1 deletion variants. We show that a frequent deletion of residues 79-89 severely reduces the ability of Nsp1 to inhibit translation while not abrogating Nsp1 binding to the 40S. Notably, while the SARS-CoV-2 5' untranslated region enhances translation of mRNA, it does not protect from Nsp1-mediated inhibition. Finally, thermal stability measurements and structure predictions reveal a correlation between stability of the NTD and the efficiency of translation inhibition.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
FEBS Lett
Year:
2022
Document Type:
Article
Affiliation country:
1873-3468.14354
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