Abstract
Structured RNA elements may control virus replication, transcription and translation, and their distinct features are being exploited by novel antiviral strategies. Viral RNA elements continue to be discovered using combinations of experimental and computational analyses. However, the wealth of sequence data, notably from deep viral RNA sequencing, viromes, and metagenomes, necessitates computational approaches being used as an essential discovery tool. In this review, we describe practical approaches being used to discover functional RNA elements in viral genomes. In addition to success stories in new and emerging viruses, these approaches have revealed some surprising new features of well-studied viruses e.g., human immunodeficiency virus, hepatitis C virus, influenza, and dengue viruses. Some notable discoveries were facilitated by new comparative analyses of diverse viral genome alignments. Importantly, comparative approaches for finding RNA elements embedded in coding and non-coding regions differ. With the exponential growth of computer power we have progressed from stem-loop prediction on single sequences to cutting edge 3D prediction, and from command line to user friendly web interfaces. Despite these advances, many powerful, user friendly prediction tools and resources are underutilized by the virology community.
Highlights
This review illustrates the key concepts and strategies used for prediction of RNA structural elements in RNA viral sequences
Double stranded viral RNA structures could be targeted by the host innate immune response, e.g., through Protein kinase RNA-activated (PKR) (Hartmann, 2017)
RNA structures located near the 3′ end are often important in nuclear export of viral RNAs, such as the Rev response element (RRE) of human immunodeficiency virus (HIV) (Groom et al, 2009) and in replication, processing, or RNA stability (Newburn and White, 2015)
Summary
This review illustrates the key concepts and strategies used for prediction of RNA structural elements in RNA viral sequences. The roles of RNA elements in viral biology is illustrated using well-studied viruses, flaviviruses, influenza, and barley yellow dwarf virus (BYDV). We further review the structures and functions of well-characterized types of RNA elements with the emphasis on prediction approaches and their limitations. There have been several excellent recent reviews on generally predicting RNA structures, in particular relating to integrating experimental data and on 3D predictions (Cantara et al, 2014; Achar and Sætrom, 2015; Weeks, 2015; Dawson and Bujnicki, 2016; Lorenz et al, 2016; Turner and Mathews, 2016). RNA 3D structure prediction methodology and incorporation of experimental. Viral RNA Structures constraint is beyond the scope of this review, but we include examples where they have been utilized
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