title: Hormonal activation of let-7-C microRNAs via EcR is required for adult Drosophila melanogaster morphology and function.
abstract: Steroid hormones and their nuclear receptors drive developmental transitions in diverse organisms, including mammals. In this study, we show that the Drosophila steroid hormone 20-hydroxyecdysone (20E) and its nuclear receptor directly activate transcription of the evolutionarily conserved let-7-complex (let-7-C) locus, which encodes the co-transcribed microRNAs miR-100, let-7 and miR-125. These small RNAs post-transcriptionally regulate the expression of target genes, and are required for the remodeling of the Drosophila neuromusculature during the larval-to-adult transition. Deletion of three 20E responsive elements located in the let-7-C locus results in reduced levels of let-7-C microRNAs, leading to neuromuscular and behavioral defects in adults. Given the evolutionary conservation of let-7-C microRNA sequences and temporal expression profiles, these findings indicate that steroid hormone-coupled control of let-7-C microRNAs is part of an ancestral pathway controlling the transition from larval-to-reproductive animal forms.
authors.affiliation: Jordan Hall A502, Department of Biology, Indiana University, Bloomington, IN 47405, USA. chawlag@indiana.edu
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Chawla
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Sokol
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D004331:Drosophila melanogaster; D004441:Ecdysterone / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004441:Ecdysterone