Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
Curr Opin Lipidol. 2018 Jun;29(3):224-232. doi: 10.1097/MOL.0000000000000503.
Noncoding RNAs have emerged as important regulators of cellular and systemic lipid metabolism. In particular, the enigmatic class of long noncoding RNAs have been shown to play multifaceted roles in controlling transcriptional and posttranscriptional gene regulation. In this review, we discuss recent advances, current challenges and future opportunities in understanding the roles of lncRNAs in the regulation of lipid metabolism during health and disease.
Despite comprising the majority of the transcriptionally active regions of the human genome, lncRNA functions remain poorly understood, with fewer than 1% of human lncRNAs functionally characterized. Broadly defined as nonprotein coding transcripts greater than 200 nucleotides in length, lncRNAs execute their functions by forming RNA-DNA, RNA-protein, and RNA-RNA interactions that regulate gene expression through diverse mechanisms, including epigenetic remodeling of chromatin, transcriptional activation or repression, posttranscriptional regulation of mRNA, and modulation of protein activity. It is now recognized that in lipid metabolism, just as in other areas of biology, lncRNAs operate to regulate the expression of individual genes and gene networks at multiple different levels.
The complexity revealed by recent studies showing how lncRNAs can alter systemic and cell-type-specific cholesterol and triglyceride metabolism make it clear that we have entered a new frontier for discovery that is both daunting and exciting.
非编码 RNA 已成为细胞和全身脂质代谢的重要调节因子。特别是,神秘的长非编码 RNA 类已被证明在控制转录和转录后基因调控方面发挥着多方面的作用。在这篇综述中,我们讨论了在理解 lncRNA 在健康和疾病状态下脂质代谢调控中的作用方面的最新进展、当前挑战和未来机遇。
尽管构成了人类基因组转录活性区域的大部分,但 lncRNA 的功能仍知之甚少,只有不到 1%的人类 lncRNA 具有功能特征。lncRNA 被广泛定义为长度大于 200 个核苷酸的非蛋白编码转录本,通过形成 RNA-DNA、RNA-蛋白质和 RNA-RNA 相互作用来执行其功能,这些相互作用通过多种机制调节基因表达,包括染色质的表观遗传重塑、转录激活或抑制、mRNA 的转录后调节以及蛋白质活性的调节。现在人们认识到,在脂质代谢中,就像在生物学的其他领域一样,lncRNA 可以在多个不同水平上调节单个基因和基因网络的表达。
最近的研究表明 lncRNA 如何改变全身和细胞特异性胆固醇和甘油三酯代谢,这揭示了复杂性,这使得我们进入了一个令人畏惧而又令人兴奋的新发现领域。