RNA Structure-A Neglected Puppet Master for the Evolution of Virus and Host Immunity

Abstract

The central dogma of molecular biology describes the flow of genetic information from DNA to protein via an RNA intermediate. For many years, RNA has been considered simply as a messenger relaying information between DNA and proteins. Recent advances in next generation sequencing technology, bioinformatics, and non-coding RNA biology have highlighted the many important roles of RNA in virtually every biological process. Our understanding of RNA biology has been further enriched by a number of significant advances in probing RNA structures. It is now appreciated that many cellular and viral biological processes are highly dependent on specific RNA structures and/or sequences, and such reliance will undoubtedly impact on the evolution of both hosts and viruses. As a contribution to this special issue on host immunity and virus evolution, it is timely to consider how RNA sequences and structures could directly influence the co-evolution between hosts and viruses. In this manuscript, we begin by stating some of the basic principles of RNA structures, followed by describing some of the critical RNA structures in both viruses and hosts. More importantly, we highlight a number of available new tools to predict and to evaluate novel RNA structures, pointing out some of the limitations readers should be aware of in their own analyses.

Keywords: RNA structure; immune evasion; secondary structure; viral RNA; viral evolution.

Figure 1

Examples of RNA structures. (A) Structural diagram of the hepatitis C virus IRES structure, showing its pseudoknot. Adapted from Malygin et al.(4), (B) Structural model of the HIV-1 5'leader RNA, highlighting some of the important RNA structures it contains. Adapted from Kenyon et al. (5), (C) An RNA guanine quadruplex structure, showing the 4-way bonds between guanines in each plane. Adapted from Frees et al. (6).