Light-regulated translational control of circadian behavior by eIF4E phosphorylation

Nat Neurosci. 2015 Jun;18(6):855-62. doi: 10.1038/nn.4010. Epub 2015 Apr 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Behavior, Animal / radiation effects
  • Brain Chemistry / genetics
  • Brain Chemistry / physiology
  • Circadian Rhythm / physiology*
  • Circadian Rhythm / radiation effects
  • Eukaryotic Initiation Factor-4E / physiology*
  • Gene Expression Regulation / radiation effects
  • Light
  • MAP Kinase Signaling System / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / physiology
  • Phosphorylation
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / physiology


  • Eukaryotic Initiation Factor-4E
  • Per1 protein, mouse
  • Per2 protein, mouse
  • Period Circadian Proteins