The Circadian Protein Nocturnin Regulates Metabolic Adaptation in Brown Adipose Tissue

Abstract

Fine-tuning of transcriptional responses can be critical for long-term outcomes in response to an environmental challenge. The circadian protein Nocturnin belongs to a family of proteins that include exonucleases, endonucleases and phosphatases and is most closely related to the CCR4 family of deadenylases that regulate the cellular transcriptome via control of polyA tail length of RNA transcripts. In this study, we investigate the role of Nocturnin in regulating the transcriptional response and downstream metabolic adaptations during cold exposure in brown adipose tissue. We find that Nocturnin exhibits dual localization within the cytosol and mitochondria, and loss of Nocturnin causes changes in expression of networks of mRNAs involved in mitochondrial function. Furthermore, Nocturnin-null animals display significantly elevated levels of TCA cycle intermediates indicating that they have distinct metabolic adaptations during a prolonged cold exposure. We conclude that Nocturnin’s role in multiple cellular compartments allows for coordinated metabolic response to environmental challenges.