Xrn1-resistant RNA structures are well-conserved within the genus flavivirus

Subgenomic RNAs are produced by several RNA viruses through incomplete degradation of their genomic RNA by the exoribonuclease Xrn1, and have been shown to be essential for viral growth and pathogenicity. Within the flavivirus genus of theFlaviviridaefamily, two distinct classes of Xrn1-resistant RNA motifs have been proposed; one for mosquito-borne and insect-specific flaviviruses, and one for tick-borne flaviviruses and no-known-vector flaviviruses. We investigated tick-borne and no-known-vector flavivirus Xrn1-resistant RNA motifs through systematicin vitromutational analysis and showed that both classes actually possess very similar structural configurations, including a double pseudoknot and a base-triple at identical, conserved locations. For the no-known-vector flavivirus Modoc virus, we show thatin vivogeneration of subgenomic flaviviral RNA was affected by mutations targeted at nucleotides involved in the structural features of flaviviral Xrn1-resistant RNA motifs that were defined in this work. Our results suggest that throughout the genus flavivirus Xrn1-resistant RNA motifs adopt the same topologically conserved structure.

Automated summary

Subgenomic RNAs are essential for viral growth and pathogenicity, and within the flavivirus genus, two classes of Xrn1-resistant RNA motifs have similar structural configurations. Mutational analysis on tick-borne and no-known-vector flaviviruses showed that mutations targeting nucleotides involved in the structure features of Xrn1-resistant RNA motifs can affect the generation of subgenomic flaviviral RNA in vivo.