Light-regulated translational control of circadian behavior by eIF4E phosphorylation.
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.
Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
Ruifeng
R
Cao
Patrick Wild Centre, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Christos G
0000000162813419
CG
Gkogkas
Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Canada.
Nuria
0000000248657752
N
de Zavalia
Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Ian D
ID
Blum
Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
Akiko
A
Yanagiya
Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
Yoshinori
Y
Tsukumo
Department of Biological Sciences, University of Memphis, Memphis, Tennessee, USA.
Haiyan
H
Xu
Department of Biomedical Sciences, Neuroscience Program, College of Medicine, Florida State University, Tallahassee, Florida, USA.
Choogon
C
Lee
Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Kai-Florian
KF
Storch
Department of Biological Sciences, University of Memphis, Memphis, Tennessee, USA.
Andrew C
AC
Liu
Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Canada.
Shimon
S
Amir
Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, Canada.
Nahum
N
Sonenberg
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology* / Q000528:radiation effects; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D005786:Gene Expression Regulation / Q000528:radiation effects; D008027:Light; D020935:MAP Kinase Signaling System / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000502:physiology
D039561:Eukaryotic Initiation Factor-4E; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins