Circadian Control of Protein Synthesis

Daily rhythms in the rate and specificity of protein synthesis occur in most mammalian cells through an interaction between cell-autonomous circadian regulation and daily cycles of systemic cues. However, the overall protein content of a typical cell changes little over 24 h. For most proteins, translation appears to be coordinated with protein degradation, producing phases of proteomic renewal that maximize energy efficiency while broadly maintaining proteostasis across the solar cycle. We propose that a major function of this temporal compartmentalization-and of circadian rhythmicity in general-is to optimize the energy efficiency of protein synthesis and associated processes such as complex assembly. We further propose that much of this temporal compartmentalization is achieved at the level of translational initiation, such that the translational machinery alternates between distinct translational mechanisms, each using a distinct toolkit of phosphoproteins to preferentially recognize and translate different classes of mRNA.