title: ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm.
abstract: It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian transcription of thousands of genes, including Per and Cry family genes that encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious rhythms in their de novo transcription, indicating the potential importance of post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme. RNA-seq showed circadian rhythms of ADARB1-mediated A-to-I editing in a variety of transcripts. In Adarb1-knockout mice, rhythms of large populations of mRNA were attenuated, indicating a profound impact of ADARB1-mediated A-to-I editing on RNA rhythms. Furthermore, Adarb1-knockout mice exhibited short-period rhythms in locomotor activity and gene expression. These phenotypes were associated with abnormal accumulation of CRY2. The present study identifies A-to-I RNA editing as a key mechanism of post-transcriptional regulation in the circadian clockwork.
authors.affiliation: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Terajima
authors.affiliation: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Yoshitane
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Haruka
authors.identifier: 0000-0002-1606-2762
authors.initials: H
authors.lastname: Ozaki
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Health Science, School of Pharmacy, Nihon University, Chiba, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimba
authors.affiliation: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Iwasaki
authors.affiliation: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukada
mesh_terms: D000241:Adenosine / Q000235:genetics*; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007288:Inosine / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: C497397:Arnt protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D016601:RNA-Binding Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D007288:Inosine; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine