title: Circadian rhythm of RNA N6-methyladenosine and the role of cryptochrome.
abstract: Methylation of RNA N(6)-methyladenosine has fundamental cellular functions, including translation regulation, RNA export, and stem cells renewal. However, the regulation of RNA N(6)-methyladenosine methylation is poorly understood. Here, we observed a robust circadian rhythm in N(6)-methyladenosine modifications of RNA. Deficiency of core mammalian clock genes, cryptochromes, decreased the levels of N(6)-methyladenosine in RNA. Cryptochrome1/2 knockout mice had significantly lower N(6)-methyladenosine methylation of RNA and lost the circadian rhythm of N(6)-methyladenosine levels in RNA. Global analysis of the circadian methylomes of N(6)-methyladenosine in RNA revealed that gene transcription, translation regulation, and RNA metabolism were highly correlated with N(6)-methyladenosine oscillation. Our findings extended a fundamental link between the circadian rhythm and N(6)-methyladenosine modification of RNA and suggested that this link is critical in controlling post-transcriptional gene expression and RNA metabolism.
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan. Electronic address: cwang@ocean.ag.
authors.forename: Chao-Yung
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors.forename: Jih-Kai
authors.initials: JK
authors.lastname: Yeh
authors.affiliation: Department of Infectious Diseases, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors.forename: Shian-Sen
authors.initials: SS
authors.lastname: Shie
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Hsieh
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000172:deficiency / Q000235:genetics*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D012313:RNA; C010223:N-methyladenosine; D000241:Adenosine
keywords: Circadian rhythm; Cryptochrome; N6-methyladenosine; RNA