RNA-mediated degradation of microRNAs: A widespread viral strategy?

The use of RNAs to regulate small RNAs, including microRNAs, is a ubiquitous feature of gene regulatory system that can be exploited by viruses. Examples of this have been described in three different herpesviruses, where viral non-coding RNAs bind to highly abundant cellular miRNAs, mediating their degradation: miR-27 is targeted by both murine cytomegalovirus and herpesvirus saimiri, while the miR-17 family is targeted by human cytomegalovirus. We review what is known about RNA-mediated regulation of miRNA stability and propose three potential roles that viral non-coding RNAs might assume to initiate the destruction of a miRNA, acting as “recruiters”, “localizers” or “exposers”. Whereas the miRNAs (miR-17 and miR-27) appear to be ancient and pre-date the common ancestor of all mammalian herpesviruses, comparative analyses of herpesvirus genomes indicate that the three known viral regulators of miRNA each evolved independently, and much more recently. Noting that the anti-viral activity of miRNAs might be countered by a variety of mechanisms, we propose that (i) there has been continual turnover of these mechanisms during herpesvirus evolution, and (ii) there may be many other, as yet undescribed, anti-miRNA activities encoded by other herpesviruses and indeed by viruses from other families.