Posttranscriptional Regulation of Mammalian Circadian Clock Output

Circadian clocks are present in many different cell types/tissues and control many aspects of physiology. This broad control is exerted, at least in part, by the circadian regulation of many genes, resulting in rhythmic expression patterns of 5-10% of the mRNAs in a given tissue. Although transcriptional regulation is certainly involved in this process, it is becoming clear that posttranscriptional mechanisms also have important roles in producing the appropriate rhythmic expression profiles. In this chapter, we review the available data about posttranscriptional regulation of circadian gene expression and highlight the potential role of Nocturnin (Noc) in such processes. NOC is a deadenylase-a ribonuclease that specifically removes poly(A) tails from mRNAs-that is expressed widely in the mouse with high-amplitude rhythmicity. Deadenylation affects the stability and translational properties of mRNAs. Mice lacking the Noc gene have metabolic defects including a resistance to dietinduced obesity, decreased fat storage, changes in lipid-related gene expression profiles in the liver, and altered glucose and insulin sensitivities. These findings suggest that NOC has a pivotal role downstream from the circadian clockwork in the posttranscriptional regulation genes involved in the circadian control of metabolism.