RNA interference and small interfering RNAs.

The term aRNA interferenceo (RNAi) was coined after the groundbreaking discovery that injection of double-stranded RNA (dsRNA) into the nematode Caenorhabditis elegans leads to specific silencing of genes highly homologous in sequence to the delivered dsRNA. The RNAi phenotype is either identical to the genetic null mutant or resembles an allelic series of mutants. The dsRNA can also be delivered by feeding bacteria that express dsRNA from recombinant plasmids to the worm or by soaking the worm in a solution containing the dsRNA. 3] In rapid sequence, RNAi was observed in other animals including mice, 5] and therefore this process possibly exists also in humans. RNAi appears to be related to the posttranscriptional gene silencing (PTGS) mechanism of cosuppression in plants and quelling in fungi. Cosuppression is the ability of some transgenes to silence both themselves and homologous chromosomal loci simultaneously. The initiator molecule for cosuppression is believed to be aberrant RNA, possibly dsRNA, and some components of the RNAi machinery are required for posttranscriptional silencing by cosuppression. 8, 13] The natural function of RNAi and cosuppression is thought to be protection of the genome against invasion by mobile genetic elements such as transposons and viruses, which produce aberrant RNA or dsRNA in the host cell when they become active. Thus, specific mRNA degradation is thought to prevent transposon and virus replication. This minireview will highlight recent advances in understanding the molecular mechanism of RNAi and its biological function. The reader is also referred to a number of excellent reviews that have appeared recently (see refs. [18 ± 24]).