Professor Cao Haiming from the National Institutes of Health in the United States focuses on the complex regulation mechanisms of energy metabolism and reveals the pathogenesis of metabolic diseases. The team has made a series of breakthrough discoveries in the analysis of the regulation of lncRNA in the field of metabolic diseases in mice. Recently, the laboratory used the Arraystar Mouse LncRNA chip to study mRNA and LncRNA in key metabolic organs of mice under pathological metabolic conditions, and screened for tissue-specific lncRNA under different metabolic conditions in mice. By overexpressing and knocking out lncRNA-Gm16551, it was elucidated that lncRNA-Gm16551 is a negative regulator of the metabolic transcription factor SREBP1c and lipogenesis. The research results were published in Cell Metabolism, the authoritative journal of cellular metabolism (impact factor 17.56). ( Chip experiments are provided by Arraystar)
Research Background:
Material and energy metabolism is one of the most basic characteristics of life, and maintaining metabolic balance is the most basic requirement of life activities. The key metabolic organs of mammals systematically regulate the energy balance of the body through the transmission and regulation of signals by endocrine factors. In addition, the energy metabolism state of the body can also systematically affect the processes of immune response, fertility, disease pathology and the like. Long-chain non-coding RNAs are a class of RNAs that are more than 200 nt in length and do not encode proteins, which have attracted the attention of the scientific community in recent years. LncRNA affects many cellular functions, including chromatin modification, transcriptional regulation, RNA stability, and translational regulation. However, the role of LncRNA in energy metabolism activities remains unknown. Therefore, it is of great research and application value to identify important lncRNA metabolic regulators and explore how lncRNA functions in disease metabolic pathways.
Research ideas:
In order to systematically study the role of lncRNA in regulating energy metabolism, the authors first used Arraystar Mouse LncRNA microarray to study the expression of lncRNA and mRNA in key metabolic organs of mice under metabolic pathophysiological conditions. The study found that 359 tissue-specific and metabolically sensitive lncRNAs in 4759 up-regulated lncRNAs were found to function in many aspects of energy metabolism through lncRNA-mRNA correlation analysis. Functional prediction of lncRNA and use of cellular experiments to study the function of target lncRNA in specific metabolic pathways. This method obtained a tissue-specific lncRNA metabolic regulator population and identified a specific lncRNA-Gm16551 involved in the regulation of hepatic lipid metabolism, which was up-regulated by the major lipid transcription factor SREBP1c; using lncRNA-Gm16551 knockout mice The test revealed that the key lipogenic genes were up-regulated and the level of triglyceride metabolism was increased. These findings suggest that lncRNA involvement constitutes an important component of nutrient sensing and metabolic response.
Technical route:
The results show:
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Figure A: Distribution of tissue-specific mRNA (top panel) and lncRNA (bottom panel) in liver (left), fat (middle) and muscle (right) under different metabolic conditions in mice
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Figure B: Association of differentially sensitive lncRNAs in the biological process of mRNA in the liver GO analysis
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Figure C: Changes in expression levels of LncRNA after 24 h of overexpression of the metabolic transcription factor SREBP1c in liver tissue
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Figure D: Changes in downstream regulatory gene expression levels in knockdown or overexpression of SREBP1c and lncRNA-Gm16551 in mouse liver tissue
Significance:
This study used Arratstar Mouse LncRNA chip technology to screen and establish a complex lineage of lncRNA associated with metabolic regulation, and then combined with bioinformatics methods and experimental analysis methods to elucidate the function of lncRNA involved in metabolic homeostasis. The results of this study strongly support the fact that lncRNA is an important component of nutrient perception and metabolic response as an important metabolic regulator in the mouse model, which lays a foundation for the functional study of lncRNA in human metabolic diseases.
Paper link:
Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators. http://dx.doi.org/10.1016/j.cmet.2016.08.019
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