Format

Send to

Choose Destination
Nat Genet. 2017 Jan;49(1):146-151. doi: 10.1038/ng.3731. Epub 2016 Nov 28.

ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm.

Author information

1
Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
2
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
3
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
4
Department of Health Science, School of Pharmacy, Nihon University, Chiba, Japan.

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.

PMID:
27893733
DOI:
10.1038/ng.3731
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center