RNA silencing

RNA silencing is a newly discovered mechanism of genetic regulation in eukaryotes. It is based on an immune system that protects eukaryotes against viruses and transposons and in some respects it is conceptually similar to classical humoral immunity. However RNA silencing is distinct from humoral immunity in that it only targets nucleic acids and has a specificity mechanism based on nucleic acid base pairing rather than on interactions with protein antibodies. Five years ago the evidence for RNA silencing was based on mysterious experimental observations in plants, a fungus and in Caenorhabditis elegans. Today we know that this process has natural biological roles and we have an outline understanding of the mechanisms. In addition RNA silencing is part of powerful enabling technologies for functional genomics. The story of this recent progress is revealing about the way that science accommodates and adapts to unexpected results. It also illustrates the power of combined molecular, genetic and biochemical approaches to problems in biology. Several terms are used to describe RNA silencing. These include ‘cosuppression’, ‘RNA interference’, ‘post-transcriptional gene silencing’, ‘sense suppression’ and ‘quelling’. Here I use ‘RNA silencing’ generically; the other terms are useful in more specific examples of RNA silencing. For example, ‘cosuppression’ refers to the specific case of RNA silencing in which RNAs of a transgene and homologous endogenous gene are co-ordinately suppressed; ‘quelling’ is cosuppression in Neurospora crassa; ‘RNA interference’ occurs when direct introduction of a double stranded RNA causes specific silencing of a homologous endogenous gene.