The Circadian Protein Nocturnin Regulates Metabolic Adaptation in Brown Adipose Tissue
Yasemin Onder,
Isara Laothamatas,
Stefano Berto,
Katharina Sewart,
Gokhul Kilaru,
Bogdan Bordieanu,
Jeremy J. Stubblefield,
Genevieve Konopka,
Prashant Mishra,
Carla B. Green
Affiliations
Yasemin Onder
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Isara Laothamatas
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Stefano Berto
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Katharina Sewart
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Gokhul Kilaru
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Bogdan Bordieanu
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Jeremy J. Stubblefield
Department of Cell Systems & Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA
Genevieve Konopka
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Prashant Mishra
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; The Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding author
Carla B. Green
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding author
Summary: 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 poly(A) 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−/− animals display significantly elevated levels of tricarboxylic acid cycle intermediates, indicating that they have distinct metabolic adaptations during a prolonged cold exposure. We conclude that cold-induced stimulation of Nocturnin levels can regulate long-term metabolic adaptations to environmental challenges. : Biological Sciences; Cell Biology; Metabolomics; Transcriptomics. Subject Areas: Biological Sciences, Cell Biology, Metabolomics, Transcriptomics
