RNA interference, or RNAi. When a gene is to be expressed, it sends instructions to the cell’s protein synthesis machinery. The intermediary is messenger RNA (mRNA), which has a structure complementary to that of the gene. In their paper, published in Nature in 1998, Fire and Mello, and colleagues, demonstrated that these mRNAs can be targeted for destruction by specific double-stranded forms of RNA (A. Fire et al , Nature 391,806-811; 1998).
It was already known that ‘antisense’ RNA — an artificial molecule whose sequence complements the mRNA could silence specific genes when taken up by a cell. But the effect was modest and inconsistent. And, to complicate the picture the same effect was obtained with ‘sense’ RNA.
In a series of experiments on a muscle gene in the nematode worm Caenorhabditis elegans Fire and Mello showed that a powerful and consistent effect required the sense and antisense RNAs to be stuck together, as double-stranded RNA. When injected with the double-stranded RNA, the worms twitched awkwardly, just like mutant worms lacking the muscle gene. The researchers also showed that mRNA was destroyed by the treatment, rather than being masked as others had believed. And they showed that the double stranded RNA can cause more copies of itself to be made, can spread between cells and can even be inherited by progeny. It is now known that organisms use this mechanism to control the expression of their genes. RNAi is an important way to control genes which insert themselves throughout the genome, jumping genes and disrupt gene function .
This mechanism of RNAi is a universal mechanism throughout all the species studied.
Nature collection December 2006
- Martin Eastwood