tetano
Editor, Senior Moderator
Nucleic Acids Res
. 2023 Jul 28;gkad627.
doi: 10.1093/nar/gkad627. Online ahead of print. SARS-CoV-2 NSP1 induces mRNA cleavages on the ribosome
Yann Tardivat[SUP] 1 [/SUP], Piotr Sosnowski[SUP] 1 [/SUP], Antonin Tidu[SUP] 1 [/SUP], Eric Westhof[SUP] 1 [/SUP], Gilbert Eriani[SUP] 1 [/SUP], Franck Martin[SUP] 1 [/SUP]
Affiliations
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to the mRNA entry channel of the ribosome and, together with the 5'-untranslated region (UTR) of the viral mRNAs, allows the evasion of that inhibition. Here, we show that NSP1 mediates endonucleolytic cleavages of both host and viral mRNAs in the 5'UTR, but with different cleavage patterns. The first pattern is observed in host mRNAs with cleavages interspersed regularly and close to the 5' cap (6-11 nt downstream of the cap). Those cleavage positions depend more on the position relative to the 5' cap than on the sequence itself. The second cleavage pattern occurs at high NSP1 concentrations and only in SARS-CoV-2 RNAs, with the cleavages clustered at positions 45, 46 and 49. Both patterns of cleavage occur with the mRNA and NSP1 bound to the ribosome, with the SL1 hairpin at the 5' end sufficient to protect from NSP1-mediated degradation at low NSP1 concentrations. We show further that the N-terminal domain of NSP1 is necessary and sufficient for efficient cleavage. We suggest that in the ribosome-bound NSP1 protein the catalytic residues of the N-terminal domain are unmasked by the remodelling of the α1- and α2-helices of the C-terminal domain.
. 2023 Jul 28;gkad627.
doi: 10.1093/nar/gkad627. Online ahead of print. SARS-CoV-2 NSP1 induces mRNA cleavages on the ribosome
Yann Tardivat[SUP] 1 [/SUP], Piotr Sosnowski[SUP] 1 [/SUP], Antonin Tidu[SUP] 1 [/SUP], Eric Westhof[SUP] 1 [/SUP], Gilbert Eriani[SUP] 1 [/SUP], Franck Martin[SUP] 1 [/SUP]
Affiliations
- PMID: 37503833
- DOI: 10.1093/nar/gkad627
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to the mRNA entry channel of the ribosome and, together with the 5'-untranslated region (UTR) of the viral mRNAs, allows the evasion of that inhibition. Here, we show that NSP1 mediates endonucleolytic cleavages of both host and viral mRNAs in the 5'UTR, but with different cleavage patterns. The first pattern is observed in host mRNAs with cleavages interspersed regularly and close to the 5' cap (6-11 nt downstream of the cap). Those cleavage positions depend more on the position relative to the 5' cap than on the sequence itself. The second cleavage pattern occurs at high NSP1 concentrations and only in SARS-CoV-2 RNAs, with the cleavages clustered at positions 45, 46 and 49. Both patterns of cleavage occur with the mRNA and NSP1 bound to the ribosome, with the SL1 hairpin at the 5' end sufficient to protect from NSP1-mediated degradation at low NSP1 concentrations. We show further that the N-terminal domain of NSP1 is necessary and sufficient for efficient cleavage. We suggest that in the ribosome-bound NSP1 protein the catalytic residues of the N-terminal domain are unmasked by the remodelling of the α1- and α2-helices of the C-terminal domain.