Abstract：
A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.
摘要：
通过高通量测序技术已经发现了各种各样的长链非编码RNA(lncRNAs),其中一些已经被证明在脂质代谢调节中起重要作用。在我们的研究中,我们发现了一种高表达的lncRNA(lnc-LLMA,肝脏脂质代谢相关的lncRNA）在杜洛克猪的肝脏中，在细胞核中富集。它在不同猪品种之间显示出有效的组织特异性。lnc-LLMA的过表达可导致猪原代肝细胞和HepG2细胞中细胞内甘油三酯(TG)水平下降和ATP和线粒体DNA水平增加。此外,MTTP的表达水平，APOB,CPT1α,lnc-LLMA的过表达增加了其他基因。它下调G6Pase和SREBP1基因的表达。通过RNA纯化（ChRIP）实验分离染色质表明，微粒体甘油三酯转移蛋白（MTTP）和糖原合酶2（GYS2）是lnc-LLMA的潜在相互作用蛋白。GYS2基因的过表达挽救了由lnc-LLMA的增加引起的细胞内TG水平的降低。同样，MTTP的过表达也能够挽救lnc-LLMA诱导的细胞内TG降低。我们的研究表明，这种新型lncRNA与脂质代谢密切相关，并通过MTTP和GYS2影响脂质转运和线粒体功能。我们的研究结果为进一步研究lncRNA在脂质代谢调控中的作用提供了新的方向。
