A Long Non-Coding RNA,GM2788,Regulates Hapatic Lipid Metabolism In Mice

Long non-coding RNAs(LncRNAs)are transcripts over 200 nucleotides,which do not have protein-coding potential.In recent years,many lncRNAs have beenidentified as key regulators of many biological processesand pathogenesis of human diseases includingcancer,cardiovascular disease,and diabetes through transcription andpost-transcription regulation.Liver is a center organ which controls glucose and lipid metabolism.The abnormal accumulation of fat in liver can lead tofatty liver diseases.However,the detailed molecular mechanisms of hepatic lipid metabolism in obesity is not fully understood.In this study,we investigate the molecular mechanism of lncRNA GM2788 in the regulation of fatty liver disease in obesity.Many mothods and technologies including RNA-seq ananlysis,qRT-PCR,RACE,in vitro translation assay,adenovirus purification,luciferase assay,and RNA pull-down are applied.The main results are listed:1.RNA-seq analysis and qRT-PCR showLncRNA GM2788 is exclusively expressed in the liver and its expression is significantly decreasedin the liver of ob/ob mice2.RACE data shows that the length of GM2788 is 893 nt.It is located in the chromosome 7 forward strand of mice.In vitro translation assaydemonstrates that GM2788 has no protein-coding potential.GM2788 is located in both nucleus and cytosol.3.Liver-specific overexpressionof lncRNA GM2788 in ob/ob mice significantly decreases liver TG levels.Consistently,in vitro cell culture experiments show that overexpression of lncRNA GM2788 decreases lipogenesis related genes expression(FASN,SCD1,GPAT1)in hepatocytes.GM2788 dose-dependently reduces FASN luciferase activity in 293 A cells.4.RNA pull-down and mass spectrometry show that pur_? interacts with lncRNA GM2788.In summary,we identify a new lncRNA GM2788 as a novel regulator of hepatic lipid metabolism in obesity.