RNAi

Mechanism by which small RNA molecules can selectively and reversibly silence a specific gene.

RNA interference had been described in different guises and given different names before it was recognized as a widespread phenomenon. In a breakthrough discovery honoured by the 2006 Nobel prize in physiology or medicine, US geneticists Andrew Fire (1959– ) and Craig Mello (1960– ) demonstrated in 1998 that double-stranded RNA (dsRNA) is necessary to achieve the full extent of gene silencing. Working with nematode worms, they also showed that the effect was targeted specifically at mature messenger RNAs (mRNAs) matching the sequence of the dsRNA, that injection of a small number of dsRNAs was sufficient to silence a larger number of mRNAs, and that the dsRNA disappeared in the process.

Within a few years, researchers uncovered the details of the process. An enzyme called dicer first cuts longer pieces of dsRNA down to fragments of 21–23 base pairs, referred to as small interfering RNAs (siRNAs). These then guide a large complex known as RISC (RNA-induced silencing complex) towards the matching mRNA. RISC contains an enzyme that will degrade the targeted mRNA.

RNAi is believed to be an important part of the anti-viral defence of plants, worms, and insects. It has also been suggested that the process may be vital for vertebrates to keep mobile genetic elements (transposons) under control and to regulate development. The full extent of the roles that RNAi plays in vertebrate organisms remains to be elucidated. In the laboratory, RNAi has quickly established itself as a simple, efficient, and reversible way of silencing genes. Unlike in mutagenesis experiments, where the DNA of the cell is modified, this process attacks only mRNA and leaves the gene itself intact.