Circadian rhythms are the physiological changes that follow a roughly 24-hour cycle, such as the sleep-wake cycle. They are found in most living things including animals, plants and fungi. The mammalian circadian biological clock regulates metabolism via a negative transcription-translation feedback loop of clock genes. Histone protein methylation is an epigenetic modification which has been suggested to be involved in circadian clock regulation; however, the role of RNA methylation in this process is still unknown.
The most common and abundant methylated nucleoside in eukaryotic RNA is N6-methyladenosine (m6A), which accounts for more than 80% of all RNA base methylations and is present in various species (1). The methyltransferase enzyme METTL3 is part of the complex involved in catalyzing m6A formation. The biological significance of this RNA modification has been unclear, possibly due to limited detection methods.
Scientists at the Graduate School of Pharmaceutical Science, Kyoto University in Japan hypothesized that regulation of RNA splicing and processing may potentially be involved in circadian clock metabolism since it was recently observed that a small percentage of rhythmic, circadian clock driven genes, such as those in the liver, do not involve de novo transcription. This group investigated the contribution of RNA methylation in circadian clock function by exploiting the cellular “methylation potential” or the SAM/SAH ratio using 3-deazaadenosine (DAA), an inhibitor of methylation. The SAM/SAH ratio is the amount of S-adenosylmethionine (SAM, Adomet), the universal methyl donor cosubstrate, to the relative amount of its by-product, S-adenosylhomocysteine (SAH), which acts as a competitive inhibitor. The authors show that m6A RNA methylation modulates RNA processing thereby regulating biological circadian clock speed and stability (2).
Their findings are summarized below:
Source: Read more about their findings and get all of the details here: Fustin, J, et al., RNA-Methylation-Dependent RNA Processing Controls the Speed of the Circadian Clock. Cell (2013) 155,793-806.
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