Functional RNA Structures in the 3’UTR of Mosquito-Borne Flaviviruses

You might have heard of Zika virus, Dengue virus, West Nile virus, or Japanese encephalitis virus

These are Mosquito-Borne Flaviviruses (MBFVs), referring to their phylogenetic association with the genus Flavivirus, and their predominant transmission vector, mosquitoes. There are dozens of other MBFVs, that cause millions of infections in humans and animals every year, rendering MBFVs a major public health threat.

Flaviviruses are enveloped, non-segmented single-stranded (+)-sense RNA viruses and consist of a single 5’-capped, non-polyadenylated RNA of approximately 10-12 kilobases in length, referred to as gRNA. The gRNA encodes a single open reading frame (ORF), which is flanked by highly structured untranslated regions (UTRs). The flavivirus UTRs are crucially involved in the regulation of the viral life cycle, and mediate processes such as genome cyclization, replication, and immune escape.

Mechanistically, these are regulated by evolutionarily conserved RNA elements in the flavivirus UTRs. An example are exoribonuclease-resistant RNAs (xrRNAs), that stall endogenous host exoribonucleases like Xrn1, thereby prohibiting further Xrn1 progression towards the viral 3’ end and thus conferring quantitative protection of downstream nucleotides. While xrRNAs are among the best studied viral non-coding RNAs (ncRNAs), MBFVs harbor many conserved RNAs of unknown function in their UTRs.

To get a better picture and understanding of RNA structure conservation in MBFVs, we report in this book chapter the results of a comparative genomics screen in the 3'UTR of all known Mosquito-Borne Flaviviruses.

Posted by Michael T. Wolfinger on . updated