LncRNAs and Glucose Metabolism

LncRNAs and Glucose Metabolism

LncRNAs are a diverse class of ncRNAs with a broad spectrum of gene-regulatory functions. Due to their tissue-specific and dynamic expression that stands in stark contrast to their poorly understood role in gene regulation, lncRNAs were recently paraphrased as 'Dark matter of the genome'. In this project, we ask whether lncRNAs control glucose metabolism and are involved in obesity-associated loss of insulin sensitivity in liver, the major glucoregulatory oragan in mammals. Using RNA-Seq and novel lncRNA prediction algorithms, we observed that obesity alters expression of 28 annotated and 15 hitherto unknown lncRNAs in two mouse models of obesity. To identify lncRNAs causally involved in control of glucose metabolism, we also established a siRNA screening system that allows functional interrogation of >600 lncRNAs. These in vitro findings will serve as entry point for the generation of lncRNA knockout mice.