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. (C) 2015 Elsevier Inc. All rights reserved.