Abstract
Almost all cellular processes are regulated by the approximately 24 h rhythms that are endogenously driven by the circadian clock. mRNA translation, as the most energy consuming step in gene expression, is temporally controlled by circadian rhythms. Recent research has uncovered key mechanisms of translational control that are orchestrated by circadian rhythmicity and in turn feed back to the clock machinery to maintain robustness and accuracy of circadian timekeeping. Here I review recent progress in our understanding of translation control mechanisms in the circadian clock, focusing on a role for the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway in modulating entrainment, synchronization and autonomous oscillation of circadian clocks. I also discuss the relevance of circadian mTOR functions in disease.
Highlights
As explained by the central dogma of molecular biology, genetic information flows from DNA to RNA to make a functional product, a protein
We show that as the downstream targets of the mitogen-activated protein kinase (MAPK)/extracellular Signalregulated Kinase (ERK) pathway, MAPK interacting protein kinases (MNKs) phosphorylate the cap-binding protein Eukaryotic translation initiation factor 4E (eIF4E) in the suprachiasmatic nucleus (SCN)
These results demonstrate that the mTORC1 signaling is an integral part of the photic entrainment pathway that regulates light-inducible mRNA translation in the SCN, precise translational control mechanisms via S6K1 remain to be delineated
Summary
As explained by the central dogma of molecular biology, genetic information flows from DNA to RNA to make a functional product, a protein. Translational control (regulation of protein synthesis) plays a significant role in the regulation of gene expression under physiological conditions. Whereas a significant role for protein synthesis in the circadian clock was found half a century ago (Feldman, 1967, 1968), novel mechanisms of mRNA translation control are being discovered in recent years. Some of these findings have been nicely summarized in three reviews (Lim and Allada, 2013b; Green, 2018; Torres et al, 2018). I discuss the latest progress in our understanding of translational control mechanisms in the circadian clock, focusing on a critical role for the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway
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