microRNA modulation of circadian-clock period and entrainment
microRNA modulation of circadian-clock period and entrainment
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DOI：
10.1016/j.neuron.2007.05.017
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发表时间：
2007-06-07
期刊：
影响因子：
16.2
通讯作者：
Obrietan, Karl
中科院分区：
文献类型：
--
作者：
Cheng, Hai-Ying M.;Papp, Joseph W.;Obrietan, Karl
MicroRNAs(MiRNAs)是一类小的、非编码的RNAs，调节mRNA转录本的稳定性或翻译。虽然最近的研究表明miRNAs与发育和疾病有关，但miRNAs在成年哺乳动物神经系统中的表达和功能尚未得到广泛的表征。在这里，我们研究了两个大脑特异的miRNAs，miR-219和miR-132，在调节位于视交叉上核的生物钟中的作用。MiR-219是Clock和BMAL1复合体的靶标，表现出强劲的昼夜节律表达，而miR-219在体内的敲除延长了昼夜节律。MIR-132是由光携带信号通过MAPK/CREB依赖的机制诱导的，调节时钟基因的表达，并减弱光的携带效应。总而言之，这些数据揭示了作为时钟和光调节基因的miRNAs，并提供了对它们作为起搏器活动和夹带的效应器的作用的机械检验。
microRNAs (miRNAs) are a class of small, noncoding RNAs that regulate the stability or translation of mRNA transcripts. Although recent work has implicated miRNAs in development and in disease, the expression and function of miRNAs in the adult mammalian nervous system have not been extensively characterized. Here, we examine the role of two brain-specific miRNAs, miR-219 and miR-132, in modulating the circadian clock located in the suprachiasmatic nucleus. miR-219 is a target of the CLOCK and BMAL1 complex, exhibits robust circadian rhythms of expression, and the in vivo knockdown of miR-219 lengthens the circadian period. miR-132 is induced by photic entrainment cues via a MAPK/CREB-dependent mechanism, modulates clock-gene expression, and attenuates the entraining effects of light. Collectively, these data reveal miRNAs; as clock- and light-regulated genes and provide a mechanistic examination of their roles as effectors of pacemaker activity and entrainment.