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.
Original language | English |
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Pages (from-to) | 1203-1213 |
Journal | FEBS Letters |
Volume | 596 |
Issue number | 9 |
Early online date | 2022 Apr 17 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
This article is protected by copyright. All rights reserved.Subject classification (UKÄ)
- Infectious Medicine
Free keywords
- Nsp1
- SARS-CoV-2
- COVID-19
- pathogenicity
- ribosome
- translation
- virus