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
Source: PubMed

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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Available from: Hai-Ying Mary Cheng, Sep 01, 2015
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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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    ABSTRACT: This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 07/2015; DOI:10.1016/j.mce.2015.07.013 · 4.24 Impact Factor
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    • "Our findings of an association between PER3-VNTR and TOL should be replicated in an independent sample in a future study, which should control for history of shift work and transmeridian travel, as well as sleep timing and intake of caffeinated beverages during several hours prior to the testing. A future analysis of polymorphisms and epigenetic variants in other genes related to circadian rhythms and neural and synaptic plasticity could be helpful to understand in further detail the molecular correlates of planning abilities (Bhatti et al., 2014; Cheng et al., 2007; Strazisar et al., 2014), which could contribute to a more complete knowledge about normal cognitive functions and related neuropsychiatric disorders (Alaerts et al., 2009; Forero et al., 2009). "
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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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