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

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Sosnowski, Piotr | Tidu, Antonin | Westhof, Eric | Martin, Franck | Eriani, Gilbert

Edité par CCSD -

International audience. 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. Cooperative actions of a 5’UTR SL1 element and the non‐structural protein NSP1 are essential for both the inhibition of host mRNAs and for specific translation of viral mRNAs1-5. 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. It appears that precise specific molecular signatures can be found in both the RNA and the NSP1 protein6. Indeed, definite sequence motifs in the RNA correlate with sequence motifs in the protein indicating a co‐evolution between the 5’UTR and NSP1 in betacoronaviruses. In the Sarbecovirus subgenus, NSP1 sequences align very well. On the other hand, they do not align well with those of either the Merbecovirus or the Embecovirus6. Here we present mutational data on 5’UTR and NSP1 from SARS‐CoV‐2 and SARS-CoV-1 using cell‐free translation extracts. We show that some conserved key residues in the N‐terminal half of the NSP1 protein are essential for evasion to the inhibitory effect of NSP1 on translation6.

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