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microRNA miR-14 acts to modulate a positive autoregulatory loop controlling steroid hormone signaling in Drosophila
Jishy Varghese1, and
Stephen M. Cohen1,2
European Molecular Biology Laboratory, 69117 Heidelberg, Germany
The insect steroid hormone Ecdysone and its receptor play importantroles during development and metamorphosis and regulate adultphysiology and life span. Ecdysone signaling, via the Ecdysonereceptor (EcR), has been proposed to act in a positive autoregulatoryloop to increase EcR levels and sensitize the animal to ecdysonepulses. Here we present evidence that this involves EcR-dependenttranscription of the EcR gene, and that the microRNA miR-14modulates this loop by limiting expression of its target EcR.Ecdysone signaling, via EcR, down-regulates miR-14. This alleviatesmiR-14-mediated repression of EcR and amplifies the response.Failure to limit EcR levels is responsible for the many of thedefects observed in miR-14 mutants. miR-14 plays a key rolein modulating the positive autoregulatory loop by which Ecdysonesensitizes its own signaling pathway.