Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle
Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle
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miRNA let-7 对果蝇昼夜节律的调节是由调节周期介导的
DOI：
10.1038/ncomms6549
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发表时间：
2014-11-01
影响因子：
16.6
通讯作者：
Zhao, Zhangwu
中科院分区：
文献类型：
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作者：
Chen, Wenfeng;Liu, Zhenxing;Zhao, Zhangwu
microRNA介导的转录后调控越来越被认为是昼夜节律的重要组成部分。在这里，我们确定microRNA let-7，果蝇let-7复合物的一部分，作为昼夜节律调节介导的昼夜节律的调节器。let-7在时钟神经元中的过表达延长了昼夜节律周期，而let-7的缺失减弱了早晨的活动高峰和分子振荡。Let-7通过抑制Clockwork橙子（CWO）来调节昼夜节律。相反，cwo表达细胞中上调的cwo可以挽救let-7-复合物过表达的表型。此外，昼夜节律的prothoracotropic激素（PTTH）和时钟调节的20-OH蜕皮类固醇信号有助于昼夜表达let-7通过20-OH蜕皮类固醇受体。因此，我们发现了一个涉及PTTH（CLOCK的直接靶点）和PTTH驱动的miRNA let-7的调控周期。
MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCK-regulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7.