Article

microRNA Modulation of Circadian-Clock Period and Entrainment

Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
Neuron (Impact Factor: 15.98). 07/2007; 54(5):813-29. DOI: 10.1016/j.neuron.2007.05.017
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ABSTRACT 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.

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    • "4374966, Life Technologies ) were used for microRNA and mRNA, respectively, according to the manufacturer's recommended protocols. For microRNA analysis, we selected eight specific microRNA assays based on evidence for their expression in the hypothalamus (let-7a, let-7b, mir-124a, mir-132, mir-145, mir-219, mir-7, mir-9) (Sakai et al., 2013; Davis et al., 2012; Cheng et al., 2007). Due to the small amount of starting material, only biological replicates were used for analysis. "
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    • "Recent studies demonstrated that miRNAs are intricately involved in the circadian regulation of clock genes[4,6,40] and clock-controlled genes. In turn, miRNA expression is controlled by clock genes[41,42]. Our group and others have previously shown that diabetes[17], metabolic syndrome[43], and aging[44,45] are associated with dysregulation of both the central and peripheral circadian clock. "
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