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Genes & Dev. 21 (18): 2277-2282

Copyright © 2007 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

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

Abstract: The insect steroid hormone Ecdysone and its receptor play important roles during development and metamorphosis and regulate adult physiology and life span. Ecdysone signaling, via the Ecdysone receptor (EcR), has been proposed to act in a positive autoregulatory loop to increase EcR levels and sensitize the animal to ecdysone pulses. Here we present evidence that this involves EcR-dependent transcription of the EcR gene, and that the microRNA miR-14 modulates this loop by limiting expression of its target EcR. Ecdysone signaling, via EcR, down-regulates miR-14. This alleviates miR-14-mediated repression of EcR and amplifies the response. Failure to limit EcR levels is responsible for the many of the defects observed in miR-14 mutants. miR-14 plays a key role in modulating the positive autoregulatory loop by which Ecdysone sensitizes its own signaling pathway.

Key Words: Ecdysone • autorgulatory feedback loop • microRNA • steroid hormone

Received for publication May 5, 2007. Accepted for publication July 23, 2007.

1 Present address: Temasek Life Sciences Laboratory and Department of Biological Sciences, 1 Research Link, The National University of Singapore, Singapore 117604.

2 Corresponding author.

E-MAIL cohen{at}tll.org.sg; FAX 65-6872-7089.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.439807

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