Light-regulated translational control of circadian behavior by eIF4E phosphorylation.

Abstract

The circadian (~24 h) clock is continuously entrained (reset) by ambient light so that endogenous rhythms are synchronized with daily changes in the environment. Light-induced gene expression is thought to be the molecular mechanism underlying clock entrainment. mRNA translation is a key step of gene expression, but how clock entrainment is controlled at the mRNA translation level is not understood. Here we report that a light- and circadian clock-regulated MAPK/MNK pathway leads to phosphorylation of the cap-binding protein eIF4E in the mouse suprachiasmatic nucleus (SCN) of the hypothalamus, the locus of the master circadian clock in mammals. Phosphorylation of eIF4E specifically promotes translation of Period (Per) 1 and 2 mRNAs and increases the abundance of basal and inducible PER proteins, which facilitates circadian clock resetting and precise timekeeping. Together, these results highlight a critical role for light-regulated translational control in the physiology of the circadian clock.