SARS-CoV-2 Nsp1 mediated mRNA degradation requires mRNA interaction with the ribosome.

ABSTRACT: Nsp1 is a SARS-CoV-2 host shutoff factor that both represses cellular translation and promotes host RNA decay. However, it is unclear how these two activities are connected and interact with normal translation processes. Here, we performed mutational analyses of Nsp1, and these revealed that both the N and C terminal domains of Nsp1 are important for translational repression. Furthermore, we demonstrate that specific residues in the N terminal domain are required for cellular RNA degradation but not bulk translation shutoff of host mRNAs, thereby separating RNA degradation from translation repression. We also present evidence that Nsp1 mediated RNA degradation requires engagement of the ribosome with mRNA. First, we observe that cytosolic lncRNAs, which are not translated, escape Nsp1 medi

SUBMITTER: Shehata SI 

PROVIDER: S-EPMC10332192 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature