论文部分内容阅读
The mammalian circadian clock plays a fundamental role in the liver physiology.Thanks to its function of oscillator, it allows a rhythmic activation of many processes involved in the regulation of fatty acid, glucose and xenobiotic metabolisms in an anticipated manner.It is supposed that the circadian clock controls liver metabolism via the regulation of enzymes and regulators at the transcriptional level.However, some evidences suggest that the circadian clock can also act at the post-transcriptional level.Indeed, we have shown that the IRE 1 pathway of the Unfolded Protein Response (UPR) is rhythmically activated, playing an important role in liver lipid homeostasis.In addition, we showed recently that the signaling pathways regulating mRNA translation, including Target of Rapamycin (TOR) pathway, are coordinated by the circadian clock.Microarray analyses of polysomal fractions allow us to identify approximately 200 mRNA that are rhythmically translated in mouse liver.Most of these mRNA codes for ribosomal proteins, wellknown TOR regulated genes.In addition, we show that other factors involved in ribosome biogenesis are rhythmically regulated at both transcriptional and translational levels.It thus seems that the circadian clock allows the anticipation of the massive proteins and mRNA synthesis required for ribosome biogenesis before the onset of the feeding period when nutrient becomes abundant and non-limiting.A functional circadian clock is required for both phenomena.As UPR and TOR are known to be involved in several pathologies including obesity and diabetes, the potential consequence of their rhythmic activation on these pathologies will be discussed.