Light-regulated translational control of circadian behavior by eIF4E phosphorylation.
|Title||Light-regulated translational control of circadian behavior by eIF4E phosphorylation.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Cao 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|
|Date Published||2015 Jun|
|Keywords||Animals, 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 Journal||Nat. Neurosci.|
|PubMed Central ID||PMC4446158|
|Grant List||MOP 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