Circadian rhythm of RNA N6-methyladenosine and the role of cryptochrome

• Published in: Biochemical and biophysical research communications Vol. 465; no. 1; pp. 88 - 94
• Main Authors: Wang, Chao-Yung, Yeh, Jih-Kai, Shie, Shian-Sen, Hsieh, I-Chang, Wen, Ming-Shien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.09.2015
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Animals; Circadian rhythm; Circadian Rhythm - genetics; Cryptochrome; Cryptochromes - deficiency; Cryptochromes - genetics; Embryo, Mammalian; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression Regulation; Male; Methylation; Mice; Mice, Inbred C57BL; Mice, Knockout; N6-methyladenosine; Protein Biosynthesis; RNA; RNA - genetics; RNA - metabolism; Signal Transduction; Transcription, Genetic; N6-methyladenosine; Circadian rhythm; RNA; Cryptochrome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.07.135

Methylation of RNA N6-methyladenosine has fundamental cellular functions, including translation regulation, RNA export, and stem cells renewal. However, the regulation of RNA N6-methyladenosine methylation is poorly understood. Here, we observed a robust circadian rhythm in N6-methyladenosine modifications of RNA. Deficiency of core mammalian clock genes, cryptochromes, decreased the levels of N6-methyladenosine in RNA. Cryptochrome1/2 knockout mice had significantly lower N6-methyladenosine methylation of RNA and lost the circadian rhythm of N6-methyladenosine levels in RNA. Global analysis of the circadian methylomes of N6-methyladenosine in RNA revealed that gene transcription, translation regulation, and RNA metabolism were highly correlated with N6-methyladenosine oscillation. Our findings extended a fundamental link between the circadian rhythm and N6-methyladenosine modification of RNA and suggested that this link is critical in controlling post-transcriptional gene expression and RNA metabolism. [Display omitted] •N6-methyladenosine (m6A) modifications of RNA exhibit a robust circadian rhythm.•Deficiency of CRY decreases the levels of m6A modifications in RNA.•CRY1/2 knockout mice lose the circadian rhythm of m6A modifications in RNA.•Circadian m6A rhythms correlate with RNA metabolism and transcription/translation.