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Publication : A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift.

First Author  Terajima H Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  14848
PubMed ID  30287844 Mgi Jnum  J:286029
Mgi Id  MGI:6391952 Doi  10.1038/s41598-018-33114-6
Citation  Terajima H, et al. (2018) A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift. Sci Rep 8(1):14848
abstractText  In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and it orchestrates peripheral clocks in the whole body to organize physiological and behavioral rhythms. Light-induced phase-shift of the SCN clock enables synchronization of the circadian clock system with 24-h environmental light/dark cycle. We previously found that adenosine deaminase acting on RNA 2 (Adar2), an A-to-I RNA editing enzyme catalyzing rhythmic A-to-I RNA editing, governs a wide range of mRNA rhythms in the mouse liver and regulates the circadian behavior. In brain, ADAR2-mediated A-to-I RNA editing was reported to occur in various transcripts encoding ion channels and neurotransmitter receptors, which could influence neuronal function of the SCN. Here we show that ADAR2 plays a crucial role for light-induced phase-shift of the circadian clock. Intriguingly, exposure of Adar2-knockout mice to a light pulse at late night caused an aberrant phase-advance of the locomotor rhythms. By monitoring the bioluminescence rhythms of the mutant SCN slices, we found that a phase-advance induced by treatment with pituitary adenylyl cyclase-activating polypeptide (PACAP) was markedly attenuated. The present study suggests that A-to-I RNA editing in the SCN regulates a proper phase response to light in the mouse circadian system.
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