1 Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
2 Patrick Wild Centre, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
3 Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Canada.
4 Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
5 Department of Biological Sciences, University of Memphis, Memphis, Tennessee, USA.
6 Department of Biomedical Sciences, Neuroscience Program, College of Medicine, Florida State University, Tallahassee, Florida, USA.

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

Nat Neurosci. 2015 Jun;18(6):855-62

Authors: Cao R, Gkogkas CG, de Zavalia N, Blum ID, Yanagiya A, Tsukumo Y, Xu H, Lee C, Storch KF, Liu AC, Amir S, Sonenberg N

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 the manner in which clock entrainment is controlled at the level of mRNA translation is not well understood. We found that a light- and circadian clock-regulated MAPK/MNK pathway led to phosphorylation of the cap-binding protein eIF4E in the mouse suprachiasmatic nucleus of the hypothalamus, the locus of the master circadian clock in mammals. Phosphorylation of eIF4E specifically promoted translation of Period 1 (Per1) and Period 2 (Per2) mRNAs and increased the abundance of basal and inducible PER proteins, which facilitated 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.

PMID: 25915475 [PubMed - indexed for MEDLINE]