Hit two birds with one stone: the multiple properties of (viral) RNA silencing suppressors

In any organism, gene expression regulation is provided by multiple factors to maintain a harmonious development of individuals. Discovered in the late 1990s, RNA interference (RNAi) completely remodelled the way in which gene expression regulations were initially apprehended. RNAi provides fine regulation at the cellular level and allows organisms to control their development, maintain their genomic integrity and fight against different stresses like viral infection. Exogenous or endogenous double-stranded RNAs initiate RNAi and are recognized and cleaved by Dicer protein in about twenty nucleotide duplexes small RNAs (sRNAs). One strand of the duplex is loaded into a ribonucleoproteic complex, named RISC (RNA induced silencing complex), composed of at least one ARGONAUTE protein and a sRNA. Therefore, the expression of any RNA possessing the complementary siRNA sequence will be specifically silenced either at the transcriptional or post-transcriptional level. RNAi plays a prominent role in the defence against viral infection and the last two decades of research have refined our knowledge of proteins involved in this pathway. Many viruses counteract the antiviral action of RNAi through the expression of factors (VSR, Viral suppressor of RNA silencing) that were first identified on virally infected plants. However, in mammals the antiviral role of RNAi remains controversial. Indeed, viral infections are controlled by the interferon response and the antiviral action of RNAi has not been clearly demonstrated in vivo. In this review, the main modes of defence suppression used by VSR and endogenous RNAi suppressors will be presented. Finally, the role of viral non-coding RNAs (ncRNAs) acting as suppressors of RNAi will be discussed.