lin-4 and
let-7 are founding members of an extensive family of genes that produce small transcripts, termed microRNAs (miRNAs). In Caenorhabditis elegans,
lin-4 and
let-7 control the timing of postembryonic events by translational repression of target genes, permitting progression from early to late developmental programs. To identify Drosophila melanogaster miRNAs that could play similar roles in the control of developmental timing, we characterized the developmental expression profile of 24 miRNAs in Drosophila, and found 7 miRNAs that are either upregulated or downregulated in conjunction with metamorphosis. The upregulation of three of these miRNAs (
mir-100,
mir-125, and
let-7), and the downregulation of a fourth (
mir-34) requires the hormone ecdysone (Ecd) and the activity of the Ecd-inducible gene Broad-Complex. Interestingly,
mir-125 is a putative homologue of
lin-4.
mir-100, -125, and
let-7 are clustered within an 800-bp region on chromosome 2L, suggesting that these three miRNAs may be coordinately regulated via common cis-acting elements during metamorphosis. In S2 cells, Ecd and the juvenile hormone analog methoprene exert opposite effects on the expression of these four miRNAs, indicating the participation of both these hormones in the temporal regulation of
mir-34, -100, -125, and
let-7 expression in vivo.