Brona McVittie reports :: October 2007

One such trick, RNA interference, has hit the headlines since Andrew Fire (Stanford, CA) and Craig Mello (Massachusetts, MA) were jointly awarded the Nobel Prize for Medicine for their work on RNAi on the roundworm, Caenorhabditis elegans. A 1998 letter to Nature highlighted their surprise discovery.

Marjori Matzke (Gregor Mendel Institute, Vienna) points out that, “a handful of botanical labs stumbled across strange cases of gene silencing in transgenic plants” about a decade prior. Her research team published their findings in transgenic tobacco in 1989 describing how transgenes were silenced in plants with two copies, but active in plants with a single copy.

The following year, a Dutch and US group simultaneously attempted to enhance petal colour in petunia generating similarly odd results. Rather than enhancing the rich purple of the petunia flower, extra copies of the ‘purple’ gene produced a splendid variety of flowers, some with dashes of purple on white, and some completely white. When the researchers looked at RNA levels for the ‘purple’ gene, white flowers showed very low levels, leading them to conclude that the added gene somehow switched off the plant’s own copy.

Several other important findings were reported by plant researchers in the 1990s. Towards the end of the decade Fire and Mello shed light on the mechanism underlying this mysterious gene shut-down. The pair injected single-stranded sense RNA from a muscle gene into worms. Nothing happened, nor did anything happen when they instead injected antisense RNA from the same gene. But both sense and antisense RNA, administered together, made the worms begin to twitch. Antisense and sense RNA were forming double-stranded RNA (dsRNA) that intercepted translation of the muscle gene into protein.

Shortly after, David Baulcombe and Andrew Hamilton (John Innes Centre, Norwich, UK) further elaborated on the process when they realised that the dsRNA gets chopped into small fragments (siRNAs) that play a key role in gene silencing. dsRNA is ‘diced’ up by a protein called dicer. Short RNAs become single-stranded when they bind to other protein complexes, from which they protrude, sticky probes in search of complementary RNA code. Complementary mRNA on its way to become protein is intercepted and broken down. The gene in question is inactivated.

Both in plants and animals, RNAi is a natural defence against invading genetic material, whether artificially introduced, as in the above experiments, or by nature in the form of viruses. In addition, this process is one of three key ways of silencing genes throughout development. Beyond the natural role of RNAi the technology has huge implications for medicine. Being able to target and silence faulty genes holds great promise for treating diseases with a genetic component. And without the worms and the petunia, we’d be none the wiser.

Read the nobel press release