Nuclear hormone receptor regulation of microRNAs controls developmental progression.
Nuclear hormone receptor regulation of microRNAs controls developmental progression.
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DOI：
10.1126/science.1164899
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发表时间：
2009-04-03
期刊：
影响因子：
--
通讯作者：
Antebi A
中科院分区：
文献类型：
--
作者：
Bethke A;Fielenbach N;Wang Z;Mangelsdorf DJ;Antebi A
核受体响应小分子信号，如维甲酸或类固醇，激活基因表达，调节不同组织的发育。MicroRNAs通过结合mRNA转录物中的互补区来关闭细胞内靶基因的表达，它们广泛地与发育和疾病有关。在这里，我们发现线虫核受体DAF-12及其类固醇配体直接激活let-7 microRNA家族成员的启动子，下调microRNA靶标HBL-1，并驱动表皮干细胞从第二幼虫期到第三幼虫期的细胞分裂。相反，未连接的受体在发育停滞期间抑制microRNA的表达。这些发现将microRNAs确定为荷尔蒙偶联分子开关的组成部分，该开关关闭早期的发育程序，以允许后来的程序。
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 mRNA transcripts, and they have been broadly implicated in development and disease. Here we show that the C. elegans nuclear receptor DAF-12 and its steroidal ligand directly activate promoters of let-7 microRNA family members to downregulate the microRNA target hbl-1 and drive progression of epidermal stem cells from second to third larval stage patterns of cell division. Conversely, the unliganded receptor 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.
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