Welcome to Silence

Our current understanding of RNA silencing derives from experiments performed in organisms from three kingdoms, experiments that directly inspired billion-dollar investments by biotechnology and pharmaceutical companies to use RNA-silencing both to diagnose and to treat disease in humans. Both small interfering RNAs and microRNA-blocking antisense oligonucleotides are now in human clinical trials [4]. Some of the first GM plants to be produced exploited RNA silencing, although the mechanisms were not well understood at the time [5,6]. The study of RNA silencing produced enabling technology that allows each gene in a sequenced genome--even cultured human cells--to be knocked out or knocked down, providing a lifeline to functional genomics. There can be no question that RNA silencing research has had an impact!RNA silencing has excited scientists and non-scientists alike: witness front-page headlines in the American and British press [7-10], even before the Nobel Prize. Such interest, of course, reflects the power of RNA silencing as biotechnology. But equally important is that RNA silencing exemplifies the elegant creativity of natural selection. Just as we might gaze in awe at a blue whale in the ocean (how can such a creature exist?), we marvel at the simple principles and complex molecular machines that underlie RNA silencing pathways. The role of silencing as an antiviral defence in plants and invertebrates illustrates this point: it uses the sequence of the invading virus itself to define the targets to be repressed and so has infinite specificity [11]. As a defense system RNA silencing is unsurpassed.The study of RNA silencing has now travelled far from its posttranscriptional roots. The link between RNA and epigenetic silencing by chromatin modification, for example, is well established in many organisms [12]. In other developments the discovery of novel families of small silencing RNAs continues to expand the universe of guides far beyond the original microRN