The Key Features of RNA Silencing

The discovery by Fire and Mello in 1998 of sequence-specific gene silencing as a response to double-stranded RNAs (dsRNAs), termed RNA interference (RNAi), has had an enormous impact on biology. In RNAi and related pathways, small noncoding RNAs of 20–30 nucleotides (nt) guide regulatory complexes to RNA targets via base-pairing and promote the inactivation of homologous sequences by a variety of mechanisms, thereby adding a great level of complexity to the way cells regulate protein levels. These pathways, which are collectively referred to as RNA silencing, mediate biological activities that fall into two broad categories; genomic surveillance and gene regulation. RNA silencing occurs in a variety of organisms and is evolutionarily conserved. Central to these processes is small RNA generation by Dicer and inactivation of cognate RNA targets by small RNA–Argonaute complexes acting in combination with a multitude of interacting and collaborating proteins. In some systems, silencing signals are amplified and small RNAs are produced by a Dicer-independent pathway, which challenges our perception and definition of RNAi. There has been remarkable progress in our understanding of the mechanisms underlying RNAi and related silencing processes, which hails the prospect of fully deciphering the RNAi machinery.