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

TitleLight-regulated translational control of circadian behavior by eIF4E phosphorylation.
Publication TypeJournal Article
Year of Publication2015
AuthorsCao R, Gkogkas CG, de Zavalia N, Blum ID, Yanagiya A, Tsukumo Y, Xu H, Lee C, Storch K-F, Liu AC, Amir S, Sonenberg N
JournalNat Neurosci
Date Published2015 Jun
KeywordsAnimals, Behavior, Animal, Brain Chemistry, Circadian Rhythm, Eukaryotic Initiation Factor-4E, Gene Expression Regulation, Light, MAP Kinase Signaling System, Mice, Mice, Inbred C57BL, Period Circadian Proteins, Phosphorylation, Suprachiasmatic Nucleus

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.

Alternate JournalNat. Neurosci.
PubMed ID25915475
PubMed Central IDPMC4446158
Grant ListMOP 114994 / / Canadian Institutes of Health Research / Canada
MOP 13625 / / Canadian Institutes of Health Research / Canada
R01 GM066157 / GM / NIGMS NIH HHS / United States
R01 NS054794 / NS / NINDS NIH HHS / United States
R01NS054794 / NS / NINDS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States