Role for a bidentate ribonuclease in the initiation step of RNA interference

RNA interference (RNAi) is the mechanism through which double-stranded RNAs silence cognate genes(1-5). In plants, this can occur at both the transcri ptional and the post-transcriptional levels(1,2,5); however, in animals, on ly post-transcriptional RNAi has been reported to date. In both plants and animals, RNAi is characterized by the presence of RNAs of about 22 nucleoti des in length that are homologous to the gene that is being suppressed(6-8) . These 22-nucleotide sequences serve as guide sequences that instruct a mu lticomponent nuclease, RISC, to destroy specific messenger RNAs6. Here we i dentify an enzyme, Dicer, which can produce putative guide RNAs. Dicer is a member of the RNase III family of nucleases that specifically cleave doubl e-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, f ungi and mammals. The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi(9,10).