ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm
| Autor: | Hideki Terajima, Yutaka Suzuki, Yoshitaka Fukada, Haruka Ozaki, Shigeki Shimba, Shinya Kuroda, Hikari Yoshitane, Wataru Iwasaki |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Adenosine Transcription Genetic Adenosine Deaminase RNA-binding protein Biology Mice 03 medical and health sciences Cryptochrome Transcription (biology) Gene expression Genetics Animals Humans Circadian rhythm Mice Knockout Regulation of gene expression Aryl Hydrocarbon Receptor Nuclear Translocator RNA-Binding Proteins RNA Inosine Circadian Rhythm Cryptochromes Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Liver RNA editing |
| Zdroj: | Nature Genetics. 49:146-151 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3731 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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