Abstract

RNA viruses have compact multifunctional genomes. During the course of infection, the genome or its derivatives must direct translation of virus proteins, genome replication and genome packaging. To realize these multiple roles, RNA virus genomes commonly have many overlapping coding and non-coding functional elements. Overlapping functional elements have often escaped detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via, for example, mutational analysis. On the other hand, RNA viruses evolve very rapidly and there are many sequenced isolates, thus providing potential for powerful comparative genomic analyses, even within single virus species. We have been using comparative genomics to systematically identify ‘hidden’ functional elements in RNA virus genomes. Computationally identified features can then be efficiently targeted for experimental analysis. We are particularly interested in characterizing unusual translation mechanisms – such as ribosomal frameshifting, stop codon readthrough, non-AUG initiation and IRES -mediated initiation – that are so frequently used by RNA viruses for gene expression. Recent work has focused on the atypical programmed ribosomal frameshifting mechanisms utilized by the arteriviruses and the cardioviruses, and RNA polymerase slippage in the potyviruses. To further understand these mechanisms, we have also employed the emerging technique of Ribosome Profiling.