Endogenous antiviral mechanisms of RNA interference: a comparative biology perspective

RNA interference (RNAi) is a natural process that occurs in many organisms ranging from plants to mammals. In this process, double-stranded RNA or hairpin RNA is cleaved by a RNaseIII-type enzyme called Dicer into small interfering RNA duplex. This then directs sequence-specific, homology-dependent, posttranscriptional gene silencing by binding to its complementary RNA and triggering its elimination through degradation or by inducing translational inhibition. In plants, worms, and insects, RNAi is a strong antiviral defense mechanism. Although, at present, it is unclear whether RNA silencing naturally restricts viral infection in vertebrates, there are signs that this is certainly the case. In a relatively short period, RNAi has progressed to become an important experimental tool both in vitro and in vivo for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has subsequently been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. In this article we review the literature in this field, which may open doors to the many uses to which this important technology is being put, including the potential of RNAi as a therapeutic strategy for gene regulation to modulate host-pathogen interactions.