Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C-elegans developmental timing

RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA a nd involves the generation of 21 to 26 nt RNA segments that guide mRNA dest ruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal R NAs (stRNAs) of 22 nt that regulate stage-specific development. Here we sho w that inactivation of genes related to RNAi pathway genes, a homolog of Dr osophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we s how that dcr-1, alg-1, and alg-2 are necessary for the maturation and activ ity of the lin-4 and let-7 stRNAs. Our findings suggest that a common proce ssing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.