Editorial

A big award for a small RNA

By general agreement, it was only a matter of time before the work that initiated the RNA interference (RNAi) revolution would be honoured by the Nobel Prize committee. The only surprise was the speed with which the committee recognized this discovery, the effects of which have permeated so many areas of biological research.

Since the early twentieth century, biologists had noted mys-terious phenomena that were triggered by virus infection of plants. Less than 20 years ago, experiments with transgenes suggested that there were both transcriptional and post-tran-scriptional mechanisms of gene silencing, but the mechanisms were unclear. Nevertheless, researchers began to exploit the observation that the introduction of RNA into a cell could inter-fere with endogenous gene expression; it was believed that this resulted from an antisense interaction between the exogenous RNA and the messenger RNA (mRNA).

The breakthrough came when Andrew Fire, Craig Mello, and their colleagues tried to understand the RNA requirements for this reaction. Their work, published in Nature in 1998, showed that injection of double-stranded RNA, rather than single-stranded RNA, elicited a much more potent silencing response. This finding was contrary to what was expected if a simple antisense mechanism operated. The second surprise was that the reaction seemed catalytic. Finally, silencing was observed not only in the injected worm, but also in its progeny. These provocative results left no doubt that a previously unrec-ognized but powerful system of gene regulation existed.

In this collection Nature presents the original paper by Fire, Mello and colleagues, the News and Views commentary piece by Richard Wagner and Lin Sun that accompanied the original paper, and the recent Nature News story that accompanied the announcement of the prize.

Nature Publishing Group is grateful to Alnylam Pharmaceuticals, a leading developer of RNAi-based therapeutics, for sponsorship of this collection.

Angela K. Eggleston

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Sponsors: Alnylam Pharmaceuticals, Inc.

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