RNA-Methylation-Dependent RNA Processing Controls the Speed of the Circadian Clock
2013; Cell Press; Volume: 155; Issue: 4 Linguagem: Inglês
10.1016/j.cell.2013.10.026
ISSN1097-4172
AutoresJean‐Michel Fustin, Masao Doi, Yoshiaki Yamaguchi, Hida Hayashi, Shinichi Nishimura, Minoru Yoshida, Takayuki Isagawa, M. Morioka, Hideaki Kakeya, Ichiro Manabe, Hitoshi Okamura,
Tópico(s)Photosynthetic Processes and Mechanisms
ResumoThe eukaryotic biological clock involves a negative transcription-translation feedback loop in which clock genes regulate their own transcription and that of output genes of metabolic significance. While around 10% of the liver transcriptome is rhythmic, only about a fifth is driven by de novo transcription, indicating mRNA processing is a major circadian component. Here, we report that inhibition of transmethylation reactions elongates the circadian period. RNA sequencing then reveals methylation inhibition causes widespread changes in the transcription of the RNA processing machinery, associated with m6A-RNA methylation. We identify m6A sites on many clock gene transcripts and show that specific inhibition of m6A methylation by silencing of the m6A methylase Mettl3 is sufficient to elicit circadian period elongation and RNA processing delay. Analysis of the circadian nucleocytoplasmic distribution of clock genes Per2 and Arntl then revealed an uncoupling between steady-state pre-mRNA and cytoplasmic mRNA rhythms when m6A methylation is inhibited.
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