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Clinically observed deletions in SARS‐CoV‐2 Nsp1 affect its stability and ability to inhibit translation
Author(s) -
Kumar Pravin,
Schexnaydre Erin,
Rafie Karim,
Kurata Tatsuaki,
Terenin Ilya,
Hauryliuk Vasili,
Carlson LarsAnders
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14354
Subject(s) - translation (biology) , untranslated region , messenger rna , five prime untranslated region , translational efficiency , eukaryotic translation , biology , three prime untranslated region , microbiology and biotechnology , genetics , gene
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.