Post-transcriptional regulation of energy usage: glucose and lipid metabolism

National Institute On Aging

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Abstract

The studies in this Project focus on understanding the RNA-binding proteins (RBPs) and noncoding (nc)RNAs that influence energy metabolism, since the processes that generate energy become impaired with aging. Historically, we have studied the regulation of insulin production, adipogenesis, and myogenesis by RBPs and ncRNAs. GLUCOSE HOMEOSTASIS. With rising appreciation that glucose metabolism is extensively regulated at the post-transcriptional level, we continue efforts to identify regulators pancreatic cell function and glucose homeostasis. A mouse model is being generated that overexpresses HuD in neuronal and pancreatic beta cells, and another in which HuD is knocked out in the same two tissues. MITOCHONDRIA. Over the past reporting period, we have made important progress towards understanding the role and metabolism of mitochondrial function in aging and age-associated declines. In collaboration with the SardiNIA team, we identified associations between the copy numbers of mitochondrial DNA and personality traits (Oppong et al., 2022) and identified imbalanced levels of mitochondrial proteins in the gastrocnemiums muscle biopsies of persons with peripheral artery disease (Circulation Research, 2023). MYOGENESIS. During this review period, we reported that the long noncoding (lnc) RNA OIP5-AS1 was capable of directing the degradation of miR-7 through a process called TDMD (target RNA-directed microRNA degradation), which in turn promotes MYMX production during human myogenesis (Yang et al., Nucleic Acids Research, 2021). We also identified a new lncRNA (lncFAM) capable of enhancing skeletal myogenesis by recruiting HNRNPL to the promoter of MYBPC2 (Chang et al., Nucleic Acids Research, 2023). In this project area, most of our efforts focused on myogenesis, particularly the impact of myoblast senescence on myogenic regeneration, the role of different lncRNAs in human myogenesis. One of the myogenic lncRNAs we are pursuing is localized in mitochondria and modulates the processing of mitochondrial RNAs.