Temporal regulation of metamorphic processes in Drosophila by the heterochronic microRNA let-7.

摘要

The let-7 and lin-4 microRNAs belong to a class of temporally expressed, non-coding regulatory RNAs that function as heterochronic genes in the nematode C. elegans, controlling the relative timing of events during development. let-7 is highly conserved and in D. melanogaster is temporally co-regulated with the lin-4 homolog, miR-125. Little is known, however, about their requirement outside the nematode, or whether they universally control the timing of developmental processes. We have generated a D. melanogaster mutant that lacks let-7 and miR-125 activities and leads to a pleiotropic phenotype arising during metamorphosis. Loss of let-7 and miR-125 results in a defect in the maturation of neuromuscular junctions (NMJs) at adult abdominal muscles. We identify the abrupt (ab) gene, as a bona fide let-7 target and provide evidence that let-7 governs the maturation rate of abdominal NMJs during metamorphosis by regulating ab expression. We demonstrate that loss of let-7 results in a temporal delay of the terminal cell cycle exit in the wing. As in C. elegans, D. melanogaster let-7 is both necessary and sufficient for the appropriate timing of a specific cell cycle exit, indicating that its function as a heterochronic microRNA is conserved.