Nuclear Hormone Receptor Regulation of MicroRNAs Controls Developmental Progression

被引：126

作者：

Bethke, Axel ^{[1
,2
]}

Fielenbach, Nicole ^{[1
]}

Wang, Zhu ^{[3
,4
]}

Mangelsdorf, David J. ^{[3
,4
]}

Antebi, Adam ^{[1
,5
]}

机构：

[1] Baylor Coll Med, Dept Mol & Cellular Biol, Huffington Ctr Aging, Houston, TX 77030 USA

[2] Univ Osnabruck, Fachbereich Biol Chem, D-49069 Osnabruck, Germany

[3] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[5] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

来源：

SCIENCE | 2009年 / 324卷 / 5923期

关键词：

C-ELEGANS; CAENORHABDITIS-ELEGANS; DAUER FORMATION; DAF-12; IDENTIFICATION; MUTATIONS; ENCODES; MIR-48; LARVAL; LIN-14;

D O I：

10.1126/science.1164899

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：95 / 98

页数：4