Font-Cunill Berta, Arnes Luis, Ferrer Jorge, Sussel Lori, Beucher Anthony
Department of Medicine, Imperial College London, London, United Kingdom.
Department of Systems Biology, Columbia University Medical Center, New York, NY, United States.
Front Genet. 2018 Nov 6;9:524. doi: 10.3389/fgene.2018.00524. eCollection 2018.
The transcriptional programs of differentiated cells are tightly regulated by interactions between cell type-specific transcription factors and -regulatory elements. Long non-coding RNAs (lncRNAs) have emerged as additional regulators of gene transcription. Current evidence indicates that lncRNAs are a very heterogeneous group of molecules. For example, selected lncRNAs have been shown to regulate gene expression in or , although in most cases the precise underlying molecular mechanisms is unknown. Recent studies have uncovered a large number of lncRNAs that are selectively expressed in pancreatic islet cells, some of which were shown to regulate β cell transcriptional programs. A subset of such islet lncRNAs appears to control the expression of β cell-specific transcription factor (TF) genes by local -regulation. In this review, we discuss current knowledge of molecular mechanisms underlying -regulatory lncRNAs and discuss challenges involved in using genetic perturbations to define their function. We then discuss known examples of pancreatic islet lncRNAs that appear to exert -regulation of TF genes. We propose that -regulatory lncRNAs could represent a molecular target for modulation of diabetes-relevant genes.
分化细胞的转录程序受到细胞类型特异性转录因子与调控元件之间相互作用的严格调控。长链非编码RNA（lncRNA）已成为基因转录的额外调控因子。目前的证据表明，lncRNA是一类非常异质的分子。例如，已发现某些lncRNA可在体外或体内调节基因表达，尽管在大多数情况下，确切的潜在分子机制尚不清楚。最近的研究发现了大量在胰岛细胞中选择性表达的lncRNA，其中一些被证明可调节β细胞转录程序。这类胰岛lncRNA的一个子集似乎通过局部调控来控制β细胞特异性转录因子（TF）基因的表达。在本综述中，我们讨论了调控lncRNA潜在分子机制的当前知识，并讨论了利用基因扰动来定义其功能所涉及的挑战。然后，我们讨论了已知的似乎对TF基因发挥调控作用的胰岛lncRNA实例。我们提出，调控lncRNA可能代表了调节糖尿病相关基因的分子靶点。
