Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell. 2018 Jan 25;172(3):393-407. doi: 10.1016/j.cell.2018.01.011.
Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bi-directional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology with great potential to advance our understanding of normal physiology and disease.
在过去的十年中,越来越多的证据表明,许多物种的基因组广泛转录,导致产生大量的长非编码 RNA(lncRNA)。与此同时,人们现在认识到,许多类型的 DNA 调控元件,如增强子和启动子,经常启动双向转录。因此,从庞大的转录组中识别有功能的非编码转录本是 lncRNA 领域的首要任务和挑战。在这篇综述中,我们旨在为分类和阐明 lncRNA 功能提供一个概念和实验框架。我们将 lncRNA 基因座分为那些在顺式调节基因表达的基因座和那些在反式发挥功能的基因座,并提出了一种基于这些分类来剖析 lncRNA 活性的实验方法。这些进一步理解 lncRNA 的策略有望揭示新的、意想不到的生物学特性,极大地促进我们对正常生理和疾病的理解。