AI Article Synopsis
- SARS CoV-2 nonstructural protein 1 (Nsp1) inhibits host translation by blocking initiation and causing cleavage of cellular mRNAs.
- The study found that cleavage requires Nsp1 and only standard translation components, with different initiation factors needed for different mRNAs.
- Key residues in Nsp1's N-terminal domain and eIF3g's RRM domain were identified as crucial for the cleavage process, indicating their role is consistent across various mRNA types.
Article Abstract
SARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted it on β-globin, EMCV IRES and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing against involvement of a putative cellular RNA endonuclease. Requirements for initiation factors differed for these mRNAs, reflecting their requirements for ribosomal attachment. Cleavage of CrPV IRES mRNA was supported by a minimal set of components consisting of 40S subunits and eIF3g's RRM domain. The cleavage site was located in the coding region 18 nucleotides downstream from the mRNA entrance indicating that cleavage occurs on the solvent side of the 40S subunit. Mutational analysis identified a positively charged surface on Nsp1's N-terminal domain (NTD) and a surface above the mRNA-binding channel on eIF3g's RRM domain that contain residues essential for cleavage. These residues were required for cleavage on all three mRNAs, highlighting general roles of Nsp1-NTD and eIF3g's RRM domain in cleavage , irrespective of the mode of ribosomal attachment.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245999 | PMC |
| http://dx.doi.org/10.1101/2023.05.25.542379 | DOI Listing |
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