@article{e4843d8d2f31432387b78311ccc785ba,
title = "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 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.",
keywords = "Biological Sciences, Cell Biology, Metabolomics, Transcriptomics",
author = "Yasemin Onder and I. Laothamatas and Stefano Berto and Katharina Sewart and Gokhul Kilaru and Bogdan Bordieanu and Stubblefield, {Jeremy J.} and Genevieve Konopka and Prashant Mishra and Green, {Carla B.}",
note = "Funding Information: We would like to acknowledge all Green lab and Mishra lab members for helpful discussions. We thank Peng Gao for sharing the pLJM1-mNOC plasmid. We acknowledge Kfir Lapid for sharing resources and helpful tips on temperature measurements, Shin Yamazaki for helpful suggestions for imaging, Katie Regan for creating the graphical abstract, and Lauren Zacharias and the UT Southwestern CRI Metabolomics Facility. This work was supported by the National Institutes of Health grants R01 GM112991 and R35 GM127122 (C.B.G.). Y.O. performed the experimental design, data collection and analysis, as well as manuscript preparation. I.L. performed the Proteinase K treatment experiment. K.S. prepared the mRNA-seq libraries and helped with mouse husbandry and genotyping. G.K. performed the mapping analysis of the mRNA-seq data. S.B. and G.K. performed bioinformatics analysis of the mRNA-seq data including the WGCNA analysis. B.B. performed the metabolomics measurements and analysis. J.J.S. and I.L. helped with tissue collections. P.M. and C.B.G. provided supervision on experimental design, data interpretation, and manuscript preparation. The authors declare no competing interests. Funding Information: We would like to acknowledge all Green lab and Mishra lab members for helpful discussions. We thank Peng Gao for sharing the pLJM1-mNOC plasmid. We acknowledge Kfir Lapid for sharing resources and helpful tips on temperature measurements, Shin Yamazaki for helpful suggestions for imaging, Katie Regan for creating the graphical abstract, and Lauren Zacharias and the UT Southwestern CRI Metabolomics Facility. This work was supported by the National Institutes of Health grants R01 GM112991 and R35 GM127122 (C.B.G.). Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = sep,
day = "27",
doi = "10.1016/j.isci.2019.07.016",
language = "English (US)",
volume = "19",
pages = "83--92",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
}