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Light-regulated translational control of circadian behavior by eIF4E phosphorylation
Ruifeng Cao1, Christos G Gkogkas2, Nuria de Zavalia3
1Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
Nature Neuroscience
|April 28, 2015
Summary
Light exposure resets the body clock by controlling mRNA translation. A specific pathway involving eIF4E phosphorylation enhances PER protein production, ensuring precise circadian timekeeping.
Area of Science:
- Neuroscience
- Molecular Biology
- Chronobiology
Background:
- The body's circadian clock synchronizes internal rhythms with environmental light-dark cycles.
- Light-induced gene expression is the known mechanism for circadian clock entrainment.
- The role of mRNA translation in circadian clock resetting remains unclear.
Purpose of the Study:
- To investigate the role of mRNA translation in circadian clock entrainment by light.
- To identify molecular mechanisms controlling translational regulation of circadian rhythms.
Main Methods:
- Studied the MAPK/MNK pathway and eIF4E phosphorylation in the mouse suprachiasmatic nucleus.
- Analyzed the effect of eIF4E phosphorylation on Period 1 (Per1) and Period 2 (Per2) mRNA translation.
- Assessed the impact on PER protein levels and circadian clock resetting.
Main Results:
- Identified a light- and circadian clock-regulated MAPK/MNK pathway.
- Demonstrated that this pathway phosphorylates eIF4E in the mouse master clock.
- Showed that phosphorylated eIF4E specifically enhances translation of Per1 and Per2 mRNAs, increasing PER proteins and facilitating clock resetting.
Conclusions:
- Light-regulated translational control plays a critical role in circadian clock physiology.
- The eIF4E phosphorylation mechanism is key for synchronizing circadian rhythms with environmental light cues.
- This finding advances understanding of the molecular basis of circadian timekeeping.
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