The temporal patterning MicroRNA let-7 regulates several transcription factors at the larval to adult transition in C-elegans
The temporal patterning MicroRNA let-7 regulates several transcription factors at the larval to adult transition in C-elegans
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DOI：
10.1016/j.devcel.2004.12.019
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发表时间：
2005-03-01
影响因子：
11.8
通讯作者：
Slack, FJ
中科院分区：
文献类型：
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作者：
Grosshans, H;Johnson, T;Slack, FJ
let-7 microRNA在许多动物中是遗传上保守的，并且在时间上表达。C.线虫let-7控制皮下组织中干细胞样谱系的终末分化，而人let-7与肺癌有关。为了阐明let-7在线虫发育的时间控制中的作用，我们使用序列分析和反向遗传学来鉴定候选let-7靶基因。我们发现核激素受体daf-12是缝细胞中let-7的靶点，而叉头转录因子pha-4是肠中的靶点。其他可能的靶点是锌指蛋白die-1和推定的染色质重塑因子Iss-4。再加上之前在腹神经索中将hunchback直系同源物hbl-1鉴定为let-7靶点，我们的研究结果表明let-7至少在三种组织中起作用，调节不同的转录因子，提高了let-7作为主要时间调节因子的可能性。
The let-7 microRNA is phylogenetically conserved and temporally expressed in many animals. C. elegans let-7 controls terminal differentiation in a stem cell-like lineage in the hypodermis, while human let-7 has been implicated in lung cancer. To elucidate let-7s role in temporal control of nematode development, we used sequence analysis and reverse genetics to identify candidate let-7 target genes. We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells, while the forkhead transcription factor pha-4 is a target in the intestine. Additional likely targets are the zinc finger protein die-1 and the putative chromatin remodeling factor Iss-4. Together with the previous identification of the hunchback ortholog hbl-1 as a let-7 target in the ventral nerve cord, our findings show that let-7 acts in at least three tissues to regulate different transcription factors, raising the possibility of let-7 as a master temporal regulator.