microRNA Modulation of Circadian-Clock Period and Entrainment

• Published in: Neuron (Cambridge, Mass.) Mass.), 2007-06, Vol.54 (5), p.813-829
• Main Authors: Cheng, Hai-Ying M., Papp, Joseph W., Varlamova, Olga, Dziema, Heather, Russell, Brandon, Curfman, John P., Nakazawa, Takanobu, Shimizu, Kimiko, Okamura, Hitoshi, Impey, Soren, Obrietan, Karl
• Format: Article
• Language: English
• Subjects: Animals; ARNTL Transcription Factors; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological Clocks - genetics; Biological Clocks - radiation effects; Brain Chemistry - genetics; Cell Line; Circadian rhythm; Circadian Rhythm - genetics; Circadian Rhythm - radiation effects; CLOCK Proteins; Dehydrogenases; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - radiation effects; Humans; Kinases; Light; MAP Kinase Signaling System - genetics; MAP Kinase Signaling System - radiation effects; Mice; MicroRNAs - genetics; MOLNEURO; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Photic Stimulation; Photoperiod; Polypeptides; Proteins; Questioning; SIGNALING; Suprachiasmatic Nucleus - anatomy & histology; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - radiation effects; SYSNEURO; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription factors; Up-Regulation - genetics; Up-Regulation - radiation effects
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.05.017

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.