SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation [article]

Katharina Schubert, Evangelos D. Karousis, Ahmad Jomaa, Alain Scaiola, Blanca Echeverria, Lukas-Adrian Gurzeler, Marc Leibundgut, Volker Thiel, Oliver Muehlemann, Nenad Ban
2020 bioRxiv   pre-print
The non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, is the first viral protein that is synthesized in SARS-CoV-2 infected human cells to suppress host innate immune functions. By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. The protein inserts its C-terminal domain at the entrance to the mRNA channel where it interferes
more » ... e it interferes with mRNA binding. We observe potent translation inhibition in the presence of Nsp1 in lysates from human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5′ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines inhibition of translation by Nsp1 with efficient translation of the viral mRNA to achieve expression of viral genes.
doi:10.1101/2020.07.07.191676 fatcat:hmwgryauorczrbgutyeqplhfcy