Onder Yasemin, Laothamatas Isara, Berto Stefano, Sewart Katharina, Kilaru Gokhul, Bordieanu Bogdan, Stubblefield Jeremy J, Konopka Genevieve, Mishra Prashant, Green Carla B
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
iScience. 2019 Sep 27;19:83-92. doi: 10.1016/j.isci.2019.07.016. Epub 2019 Jul 16.
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.
转录反应的精细调节对于应对环境挑战的长期结果可能至关重要。昼夜节律蛋白夜蛋白属于一类包括核酸外切酶、核酸内切酶和磷酸酶的蛋白质家族，并且与通过控制RNA转录本的聚腺苷酸尾长度来调节细胞转录组的脱腺苷酸酶CCR4家族关系最为密切。在本研究中，我们调查了夜蛋白在调节棕色脂肪组织冷暴露期间的转录反应和下游代谢适应中的作用。我们发现夜蛋白在细胞质和线粒体中表现出双重定位，并且夜蛋白的缺失会导致参与线粒体功能的mRNA网络表达发生变化。此外，缺乏夜蛋白的动物显示三羧酸循环中间体水平显著升高，表明它们在长时间冷暴露期间具有独特的代谢适应。我们得出结论，冷诱导的夜蛋白水平刺激可调节对环境挑战的长期代谢适应。
