Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock
Thanks to the accumulation of molecular knowledges about biological clock, we can predict a missing link “X” in the system by using a realistic simulator. Meal-time is known to influence our sleep-wake timing. But the mechanism has been unknown. This time, the group of Dr. Okamura at Kyoto University discovered a new enzyme (named, Ck1δ2) that possibly links between our metabolic system and biological clock. Based on the experimental results by Dr. Okamura, two iTHEMS members (Gibo and Kurosawa) predicted the specific biochemical process, activated by the new enzyme. The prediction was conducted by using a 190 variables model with all genes and proteins. Fortunately, the prediction was confirmed experimentally. The point for the prediction was the activation of the new enzyme “slowed” the biological clock in the experiment while the activation of most enzymes “accelerate” the clock in the simulator. Now, the mechanism is studied by using a simpler model. Then, a possible scenario is that amino-acids in our food influence our sleep-wake timing via the new enzyme.
- Jean-Michel Fustin, Rika Kojima, Kakeru Itoh, Hsin-Yi Chang, Ye Shiqi, Bowen Zhuang, Asami Oji, Shingo Gibo, Rajesh Narasimamurthy, David Virshup, Gen Kurosawa, Masao Doi, Ichiro Manabe, Yasushi Ishihama, Masahito Ikawa, Hitoshi Okamura
"Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock"
Journal Reference: Proc. Natl. Acad. Sci. USA 115, 5980-5985 (2018)