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RNA . Correlated sequence signatures are present within the genomic 5'UTR RNA and NSP1 protein in coronaviruses

tetano

Editor, Senior Moderator
RNA


. 2022 Mar 2;rna.078972.121.
doi: 10.1261/rna.078972.121. Online ahead of print.
Correlated sequence signatures are present within the genomic 5'UTR RNA and NSP1 protein in coronaviruses


Piotr Sosnowski[SUP] 1 [/SUP], Antonin Tidu[SUP] 2 [/SUP], Gilbert Eriani[SUP] 1 [/SUP], Eric Westhof[SUP] 1 [/SUP], Franck Martin[SUP] 3 [/SUP]



Affiliations

Abstract

The 5'UTR part of coronavirus genomes plays key roles in the viral replication cycle and the translation of the viral mRNAs. The first 75-80 nucleotides, also called the leader sequence, are identical for the genomic mRNA and for the subgenomic mRNAs. Recently, it was shown that cooperative actions of a 5'UTR segment and the non-structural protein NSP1 are essential for both the inhibition of host mRNAs and for specific translation of viral mRNAs. Here, sequence analyses of both the 5'UTR RNA segment and the NSP1 protein have been done for several coronaviruses with special attention to the betacoronaviruses. The conclusions are (i) precise specific molecular signatures can be found in both the RNA and the NSP1 protein; (ii) both types of signatures strongly correlate between each other. Indeed, definite sequence motifs in the RNA correlate with sequence motifs in the protein indicating a co-evolution of 5'UTR with NSP1 in betacoronaviruses. Experimental mutational data on 5'UTR and NSP1 from SARS-CoV-2 using cell-free translation extracts support those conclusions and show that the N-terminal half of the NSP1 protein contains conserved key residues that are essential for evasion to the inhibitory effect of NSP1 on translation.

Keywords: SARS-CoV-2, NSP1, SL1, 5’UTR, translation, ribosome.
 
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