RNA silencing: A remarkable parallel to protein-based immune systems in vertebrates?

Sequence-specific gene silencing by double-strand RNA has been observed in many eukaryotes. Accumulating data suggest that it is the major antiviral defense mechanism in plants and invertebrates. The discovery that this cellular mechanism is also highly conserved though somewhat impaired in mammals has stimulated debate about the evolution of antiviral systems. Here we suggest that the existence of the interferon response as an evolutionary intermediate could account for both the relative decline of RNA silencing and the development of protein-based immune systems in vertebrates. In addition, we emphasize the opportunities presented by RNA silencing and the deeper understanding of vertebrate antiviral systems that is needed.