The Novel Long Noncoding RNA Lnc19959.2 Modulates Triglyceride Metabolism Associated Genes Through Interaction with Purb and hnRNPA2B1.

Abstract Objective Long non-coding RNAs (lncRNAs) are currently consider to have vital and wide range of biological functions, but the molecular mechanism underlying triglycerides metabolism remains poorly understood. This study aims to identify novel lncRNAs differentially expressed in rat liver with hypertriglyceridemia and elucidated the function role in TG metabolism. Methods Differentially expression of lncRNAs in rat liver with hypertriglyceridemia were identified by transcriptome sequencing and validated by real-time PCR. The role of lnc19959.2 in triglyceride metabolism was assessed both in vitro and in vivo. RNA Pull down and RIP assays were conducted to evaluate the interactions between lnc19959.2 and its target proteins. ChIP and Dual report assays were performed to detects the interactions between transcription factors and promoter of its target genes. Results We identified a novel lncRNA, lnc19959.2 was up regulated in rat liver with hypertriglyceridemia. Knockdown of lnc19959.2 has profound TG lowering effects in vitro and in vivo. Subsequently genome-wide analysis identified that knockdown of lnc19959.2 caused deregulation of many genes during TG homeostasis. Further mechanism studies revealed that lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb, while specifically interacted to hnRNPA2B1 to down-regulate expression of Cpt1a, Tm7sf2 and Gpam, respectively. In the upstream pathway, palmitate acid up-regulated CCAAT/Enhancer-Binding Protein Beta (Cebpb) and facilitated its binding to promoter of lnc19959.2, which resulted in significant promotion of lnc19959.2 transcriptional activity. Conclusion Our findings provide novel insights of a new layer regulatory complexity of a lncRNA that modulating triglyceride homeostasis by a novel lncRNA lnc19959.2.