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Science 3 April 2009:
Vol. 324. no. 5923, pp. 95 - 98
DOI: 10.1126/science.1164899
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Reports

Nuclear Hormone Receptor Regulation of MicroRNAs Controls Developmental Progression

Axel Bethke,1,2 Nicole Fielenbach,1 Zhu Wang,3 David J. Mangelsdorf,3 Adam Antebi1,4*

In response to small-molecule signals such as retinoids or steroids, nuclear receptors activate gene expression to regulate development in different tissues. MicroRNAs turn off target gene expression within cells by binding complementary regions in messenger RNA transcripts, and they have been broadly implicated in development and disease. Here we show that the Caenorhabditis elegans nuclear receptor DAF-12 and its steroidal ligand directly activate promoters of let-7 microRNA family members to down-regulate the microRNA target hbl-1, which drives progression of epidermal stem cells from second to third larval stage patterns of cell division. Conversely, the receptor without the ligand represses microRNA expression during developmental arrest. These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones.

1 Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
2 University of Osnabrück, Fachbereich Biologie/Chemie, Barbarastrasse 11, 49069 Osnabrück, Germany.
3 Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
4 Max-Planck-Institute for Biology of Ageing, Gleulerstrasse 50a, D-50931 Cologne, Germany.

* To whom correspondence should be addressed. E-mail: aantebi{at}bcm.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans.
C. M. Hammell, X. Karp, and V. Ambros (2009)
PNAS 106, 18668-18673
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miRNA Regulation Through Ligand Occupancy of a Nuclear Hormone Receptor.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)