Identification and potential function of viral microRNAs

The discovery of RNA interference (RNAi) and microRNAs (miRNAs) is undoubtedly one of the most significant recent advances in the field of biology. miRNAs were initially identified in Caenorhabditis elegans with the discovery of a small RNA, lin-4, that was shown to regulate the heterochronic gene lin-14 (Lee et al., 1993; Wightman et al., 1993). Further investigations led to the identification of a second small RNA, let-7, that played a similar role in regulation of developmental genes (Reinhart et al., 2000). Subsequent studies using extensive cloning strategies and bioinformatics methods have identified hundreds of miRNA genes in plants and animals suggesting that post-transcriptional regulation through expression of small RNAs is an evolutionarily conserved and common mechanism of gene regulation (Bartel, 2004; Pfeffer et al., 2004; Pfeffer et al., 2005). More recent studies have revealed that a surprisingly large percentage of genes in higher organisms may be regulated by miRNAs (Brennecke et al., 2005; Grün et al., 2005; Krek et al., 2005; Lewis et al., 2005; Xie et al., 2005). Given the widespread prevalence and influential effects of miRNAs on gene expression it is unsurprising that viruses exploit RNAi pathways by expressing their own small RNAs. In this chapter we will review what is currently known about virally encoded miRNAs, including examination of their expression, genomic position and degree of evolutionary conservation between related viruses. We will also discuss the potential functions of viral miRNAs.