let-7 coordinates the transition to adulthood through a single primary and four secondary targets
let-7 coordinates the transition to adulthood through a single primary and four secondary targets
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DOI：
10.26508/lsa.201900335
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发表时间：
2019-04-01
影响因子：
4.4
通讯作者：
Grosshans, Helge
中科院分区：
文献类型：
--
作者：
Aeschimann, Florian;Neagu, Anca;Grosshans, Helge
青春期是动物身体形态和功能发生广泛变化的时期。青春期的开始是遗传控制的，let-7 miRNA在线虫和哺乳动物中暂时调节J/A转换事件。在这里，我们揭示了秀丽隐杆线虫let-7控制雄性和雌性性器官形态发生和皮肤祖细胞命运的靶点和下游途径。我们发现let-7通过沉默一个单一的靶点，即转录后调节因子lin-41，来指导这三个过程。反过来，RNA结合蛋白LIN 41/TRIM 71通过仅沉默四种靶mRNA来调节这些过程。因此，通过沉默LIN 41，let-7激活LIN-29 a和MAB-10（分别为早期生长反应型转录因子及其NAB 1/2-正向辅因子）以终止祖细胞自我更新并促进外阴完整性。相比之下，let-7通过上调DMD-3和MAB-3（两种含有Doublemex/MAB-3结构域的转录因子）来促进男性性器官的发育。我们的研究结果提供了一个线性链的转录后调节分歧的一小部分转录调节子的控制，以实现协调的J/A转换的机制的见解。
The juvenile-to-adult (J/A) transition, or puberty, is a period of extensive changes of animal body morphology and function. The onset of puberty is genetically controlled, and the let-7 miRNA temporally regulates J/A transition events in nematodes and mammals. Here, we uncover the targets and downstream pathways through which Caenorhabditis elegans let-7 controls male and female sexual organ morphogenesis and skin progenitor cell fates. We find that let-7 directs all three processes by silencing a single target, the post-transcriptional regulator lin-41. In turn, the RNA-binding protein LIN41/TRIM71 regulates these processes by silencing only four target mRNAs. Thus, by silencing LIN41, let-7 activates LIN-29a and MAB-10 (an early growth response-type transcription factor and its NAB1/2-orthologous cofactor, respectively) to terminate progenitor cell self-renewal and to promote vulval integrity. By contrast, let-7 promotes development of the male sexual organ by up-regulating DMD-3 and MAB-3, two Doublesex/MAB-3 domain-containing transcription factors. Our results provide mechanistic insight into how a linear chain of post-transcriptional regulators diverges in the control of a small set of transcriptional regulators to achieve a coordinated J/A transition.