RRC ID 47285
Author Terajima H, Yoshitane H, Ozaki H, Suzuki Y, Shimba S, Kuroda S, Iwasaki W, Fukada Y.
Title ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm.
Journal Nat. Genet.
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.
Volume 49(1)
Pages 146-151
Published 2017-1
DOI 10.1038/ng.3731
PII ng.3731
PMID 27893733
MeSH Adenosine / genetics* Adenosine Deaminase / genetics Adenosine Deaminase / metabolism* Animals Aryl Hydrocarbon Receptor Nuclear Translocator / physiology Circadian Rhythm / physiology* Cryptochromes / genetics Cryptochromes / metabolism Gene Expression Regulation Humans Inosine / genetics* Liver / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout RNA / genetics* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Transcription, Genetic / genetics*
IF 27.125
Times Cited 0
Human and Animal Cells NIH3T3-3-4(RCB1862)