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

Abstract 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 cir...

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Autores principales: Hideki Terajima, Hikari Yoshitane, Tomoko Yoshikawa, Yasufumi Shigeyoshi, Yoshitaka Fukada
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Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/2306fa7987464a5eb119a4d7b722dfab
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spelling oai:doaj.org-article:2306fa7987464a5eb119a4d7b722dfab2021-12-02T11:41:23ZA-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift10.1038/s41598-018-33114-62045-2322https://doaj.org/article/2306fa7987464a5eb119a4d7b722dfab2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33114-6https://doaj.org/toc/2045-2322Abstract 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.Hideki TerajimaHikari YoshitaneTomoko YoshikawaYasufumi ShigeyoshiYoshitaka FukadaNature PortfolioarticlePituitary Adenylyl Cyclase-activating Polypeptide (PACAP)ADAR2 Knockout MiceBioluminescence RhythmLight-induced Phase AdvancesmRNA RhythmMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution DOAJ
collection DOAJ
language EN
topic Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP)
ADAR2 Knockout Mice
Bioluminescence Rhythm
Light-induced Phase Advances
mRNA Rhythm
Medicine
R
Science
Q
spellingShingle Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP)
ADAR2 Knockout Mice
Bioluminescence Rhythm
Light-induced Phase Advances
mRNA Rhythm
Medicine
R
Science
Q
Hideki Terajima
Hikari Yoshitane
Tomoko Yoshikawa
Yasufumi Shigeyoshi
Yoshitaka Fukada
A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
description Abstract 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.
format article
author Hideki Terajima
Hikari Yoshitane
Tomoko Yoshikawa
Yasufumi Shigeyoshi
Yoshitaka Fukada
author_facet Hideki Terajima
Hikari Yoshitane
Tomoko Yoshikawa
Yasufumi Shigeyoshi
Yoshitaka Fukada
author_sort Hideki Terajima
title A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
title_short A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
title_full A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
title_fullStr A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
title_full_unstemmed A-to-I RNA editing enzyme ADAR2 regulates light-induced circadian phase-shift
title_sort a-to-i rna editing enzyme adar2 regulates light-induced circadian phase-shift
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/2306fa7987464a5eb119a4d7b722dfab
work_keys_str_mv AT hidekiterajima atoirnaeditingenzymeadar2regulateslightinducedcircadianphaseshift
AT hikariyoshitane atoirnaeditingenzymeadar2regulateslightinducedcircadianphaseshift
AT tomokoyoshikawa atoirnaeditingenzymeadar2regulateslightinducedcircadianphaseshift
AT yasufumishigeyoshi atoirnaeditingenzymeadar2regulateslightinducedcircadianphaseshift
AT yoshitakafukada atoirnaeditingenzymeadar2regulateslightinducedcircadianphaseshift
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