Circadian control of Nocturnin and its regulatory role in health and disease

Circadian rhythms are generated by intrinsic 24-h oscillations that anticipate the extrinsic changes associated with solar day. A conserved transcriptional-translational feedback loop generates these molecular oscillations of clock genes at the organismal and the cellular levels. One of the recently discovered outputs of circadian clock is Nocturnin (Noct) or Ccrn4l. In mice, Noct mRNA is broadly expressed in cells throughout the body, with a particularly high-amplitude rhythm in liver. NOCT belongs to the EEP family of proteins with the closest similarity to the CCR4 family of deadenylases. Multiple studies have investigated the role of Nocturnin in development, adipogenesis, lipid metabolism, inflammation, osteogenesis, and obesity. Further, mice lacking Noct (Noct KO or Noct-/-) are protected from high-fat diet-induced obesity and hepatic steatosis. Recent studies had provided new insights by investigating various aspects of Nocturnin, ranging from its sub-cellular localization to identification of its target transcripts. However, a profound understanding of its molecular function remains elusive. This review article seeks to integrate the available literature into our current understanding of the functions of Nocturnin, their regulatory roles in key tissues and to throw light on the existing scientific lacunae.