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

Nature Genetics 49, 146 (2017).
doi:10.1038/ng.3731

Authors: Hideki Terajima, Hikari Yoshitane, Haruka Ozaki, Yutaka Suzuki, Shigeki Shimba, Shinya Kuroda, Wataru Iwasaki & Yoshitaka Fukada
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.

Source: Nature Genetics - November 27, 2016 Category: Genetics & Stem Cells Authors: Hideki Terajima Hikari Yoshitane Haruka Ozaki Yutaka Suzuki Shigeki Shimba Shinya Kuroda Wataru Iwasaki Yoshitaka Fukada Tags: Letter Source Type: research