MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila.
MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila.
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DOI：
10.1038/ncomms14707
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发表时间：
2017-03-09
影响因子：
16.6
通讯作者：
Rosbash M
中科院分区：
文献类型：
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作者：
Chen X;Rosbash M
动物的许多生物和行为过程受内源性生物钟控制，而生物钟依赖于转录调控。在这里，我们讨论转录后调控和 miRNA 在果蝇昼夜节律中的作用。至少有 6 个 miRNA 在色素分散因子 (PDF) 细胞起搏神经元内显示出循环表达水平；只有 mir-92a 在夜间达到峰值。体内钙监测、PDF 投影动态、ArcLight、GCaMP6 成像和睡眠测定表明 mir-92a 抑制神经元兴奋性。此外，PDF 细胞内的 mir-92a 水平会对光脉冲做出响应，也会影响相移响应。翻译核糖体亲和纯化 (TRAP) 和体外荧光素酶报告基因测定表明 mir-92a 抑制 sirt2 的表达，sirt2 与人 Sir2 和 Sirt3 同源。 Sirt2 RNAi 还可对 mir-92a 过度表达进行表型复制。这些实验表明，sirt2 是 mir-92a 的功能性靶标，并且 mir-92a 通过有节奏地抑制 SIRT2 水平来调节 PDF 神经元兴奋性。越来越多的证据表明 microRNA 在昼夜节律调节中发挥作用。作者在此表明，在果蝇大脑中，mir-92a 通过抑制其目标 Sirt2 的翻译来抑制 PDF 神经元（果蝇中关键的昼夜节律起搏细胞）的兴奋性。
Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during the night. In vivo calcium monitoring, dynamics of PDF projections, ArcLight, GCaMP6 imaging and sleep assays indicate that mir-92a suppresses neuronal excitability. In addition, mir-92a levels within PDF cells respond to light pulses and also affect the phase shift response. Translating ribosome affinity purification (TRAP) and in vitro luciferase reporter assay indicate that mir-92a suppresses expression of sirt2, which is homologous to human sir2 and sirt3. sirt2 RNAi also phenocopies mir-92a overexpression. These experiments indicate that sirt2 is a functional mir-92a target and that mir-92a modulates PDF neuronal excitability via suppressing SIRT2 levels in a rhythmic manner. Accumulating evidence suggests that microRNAs play a role in circadian regulation. Here the authors show that in the Drosophila brain, mir-92a suppresses the excitability of PDF neurons—key circadian pacemaker cells in Drosophila—via inhibiting the translation of its target sirt2.