Abstract

It has been 11 years since the Ambros laboratory reported the first microRNA (miRNA; Lee et al. 1993), and six years since the Fire and Mello laboratories described the gene silencing effects of double-stranded RNA (dsRNA; Fire et al. 1998). It is now clear that those reports each “lifted a corner of a great veil” (to paraphrase Albert Einstein) that had previously hidden an astonishing range of gene regulatory phenomena, many of which had been hinted at in plants (Matzke and Matzke 2004) and fungi (Pickford et al. 2002). The ongoing efforts to uncover the full biological scope of RNA silencing and to develop it as an experimental and therapeutic tool came into view on April 14–19, 2004, as 540 scientists from around the globe convened in the thin air of Keystone, Colorado, for the 2004 Keystone Symposium entitled “siRNAs and miRNAs.” The attendance more than doubled that of a similar Keystone Symposium held two years earlier, attesting to the rapid growth of interest in RNA silencing. Given the ever-expanding breadth of the field, meeting organizers Victor Ambros and Tom Tuschl did an exemplary job of ensuring that there was something for everyone in attendance. The conference was loosely organized around a progression from biological roles to molecular mechanisms, and then on to more applied topics such as large-scale RNA interference (RNAi) screens and dsRNA-based therapeutics. This review will follow the same thematic format, with an emphasis on roles and mechanisms.

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