Abstract

The genus Flavivirus comprises numerous, small, single positive-stranded RNA viruses, many of which are important human pathogens. To store all the information required for their successful propagation, flaviviruses use discrete structural genomic RNA elements to code for functional information by the establishment of dynamic networks of long-range RNA–RNA interactions that promote specific folding. These structural elements behave as true cis-acting, non-coding RNAs (ncRNAs) and have essential regulatory roles in the viral cycle. These include the control of the formation of subgenomic RNAs, known as sfRNAs, via the prevention of the complete degradation of the RNA genome. These sfRNAs are important in ensuring viral fitness. This work summarizes our current knowledge of the functions performed by the genome conformations and the role of RNA–RNA interactions in these functions. It also reviews the role of RNA structure in the production of sfRNAs across the genus Flavivirus, and their existence in related viruses.

Highlights

  • The genus Flavivirus comprises numerous, small, single positive-stranded RNA viruses, many of which are important human pathogens

  • RNA genomes behave as molecules that store protein-coding information, and as non-coding RNAs, functions that together ensure the correct regulation of the viral cycle

  • This review examines our current knowledge of the structure/function of the flavivirus genome, with special attention given to the networks of interactions that occur among different structural RNA units

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Summary

Introduction

The genus Flavivirus comprises many small, enveloped viruses commonly known as flaviviruses. Besides containing protein-coding information, the flavivirus RNA genome stores essential information in structurally conserved units. These are scattered throughout the genome, with the flanking UTRs being rich in them (reviewed by [5,6]). RNA genomes behave as molecules that store protein-coding information (mRNA), and as non-coding RNAs (ncRNAs), functions that together ensure the correct regulation of the viral cycle. This multifunctional behavior is maintained by the establishment of intricate networks of RNA–RNA interactions—the RNA interactome—. Flavivirus, and their putative existence in related viruses, is provided

Structural Diversification of the Flavivirus RNA Genome
Cyclization of the Flavivirus Genome
(Figures free
Biogenesis of sfRNAs
The Role of sfRNAs
Conclusions and Perspectives
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