The novel long noncoding RNA Lnc19959.2 modulating triglyceride metabolism associated genes through interaction with Purb and hnRNPA2B1 (RNA-seq data set)

High triglycerides can lead to atherosclerotic cardiovascular disease. Long noncoding RNAs (lncRNAs) are currently consider to have vital and wide range of biological functions, but the molecular mechanism underlying TG metabolism remains poorly understood. To identify novel lncRNAs differentially expressed in rat liver with hypertriglyceridemia using transcriptome sequencing and elucidated the function role in TG metabolism. In our study, we identified a novel lncRNA, Lnc19959.2, which was highly expression in rat liver with hypertriglyceridemia. Knockdown of lnc19959.2 has profound TG lowering effects in vitro and vivo. Subsequently genome-wide analysis identified that knockdown of Lnc19959.2 caused deregulation of many genes during TG homeostasis. Further mechanism studies reveal that Lnc19959.2 specifically bound to Purb to up-regulate expression of Apoa4, while bound to hnRNPA2B1 to down-regulate the expression of Cpt1a, Tm7sf2 and Gpam, respectively. In the upstream pathway, palmitate acid up-regulated CCAAT/Enhancer-Binding Protein Beta (Cebpb) facilitates its binding to promoter region of Lnc19959.2, which resulted in significant promotion of lnc19959.2 transcriptional activity. Our findings provide novel insights into transcriptional regulation of TG homeostasis by a novel lncRNA. This newly identified lncRNA could be exploited as novel therapeutic targets for hypertriglyceridemia.高甘油三酯血症可引发动脉粥样硬化性心血管疾病。长链非编码RNA（long noncoding RNAs，lncRNAs）目前被认为具有广泛且关键的生物学功能，但甘油三酯代谢的潜在分子机制仍未得到充分解析。本研究通过转录组测序技术，筛选高甘油三酯血症大鼠肝脏中差异表达的新型长链非编码RNA，并阐明其在甘油三酯代谢中的功能作用。本研究中，我们鉴定出一种新型长链非编码RNA Lnc19959.2，其在高甘油三酯血症大鼠肝脏中呈高表达状态。敲低Lnc19959.2可在体内外产生显著的降甘油三酯效应。随后的全基因组分析显示，敲低Lnc19959.2会导致甘油三酯稳态相关的大量基因表达失调。进一步的机制研究揭示，Lnc19959.2可特异性结合嘌呤富集元件结合蛋白B（Purb）以上调载脂蛋白A4（Apoa4）的表达，同时分别结合异质性细胞核核糖蛋白A2B1（hnRNPA2B1），下调肉碱棕榈酰转移酶1a（Cpt1a）、跨膜7固醇结合蛋白2（Tm7sf2）及甘油-3-磷酸酰基转移酶（Gpam）的表达。在上游调控通路中，棕榈酸可上调CCAAT增强子结合蛋白β（Cebpb）的表达，促进其结合至Lnc19959.2的启动子区域，进而显著增强Lnc19959.2的转录活性。本研究结果为新型长链非编码RNA调控甘油三酯稳态的转录机制提供了全新视角。这一新鉴定的长链非编码RNA有望成为高甘油三酯血症的新型治疗靶点。