Nuclear hormone receptor regulation of microRNAs controls developmental progression

Axel Bethke, Nicole Fielenbach, Zhu Wang, David J. Mangelsdorf, Antebi Adam

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)95-98
Number of pages4
JournalScience
Volume324
Issue number5923
DOIs
StatePublished - Apr 3 2009

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Cytoplasmic and Nuclear Receptors
MicroRNAs
Ligands
Gene Expression
Steroid Receptors
Retinoids
Caenorhabditis elegans
Cell Division
Stem Cells
Down-Regulation
Hormones
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Nuclear hormone receptor regulation of microRNAs controls developmental progression. / Bethke, Axel; Fielenbach, Nicole; Wang, Zhu; Mangelsdorf, David J.; Adam, Antebi.

In: Science, Vol. 324, No. 5923, 03.04.2009, p. 95-98.

Research output: Contribution to journalArticle

Bethke, Axel ; Fielenbach, Nicole ; Wang, Zhu ; Mangelsdorf, David J. ; Adam, Antebi. / Nuclear hormone receptor regulation of microRNAs controls developmental progression. In: Science. 2009 ; Vol. 324, No. 5923. pp. 95-98.
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