Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02142, USA.
Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts 02142, USA.
Nat Rev Mol Cell Biol. 2016 Dec;17(12):756-770. doi: 10.1038/nrm.2016.126. Epub 2016 Oct 26.
Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples - including Xist, which orchestrates X chromosome inactivation - has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus.
在过去的十年中，人们已经清楚地认识到哺乳动物基因组编码了数千种长非编码 RNA（lncRNA），其中许多与各种生物学过程有关。最近，研究人员对包括 Xist 在内的几个关键例子的分子机制进行了研究，这些例子提供了新的见解，说明 lncRNA 如何通过在核内发挥作用来控制细胞功能。在这里，我们讨论了 lncRNA 如何通过协调调节蛋白、定位到靶标位点和塑造三维（3D）核组织来调节基因表达的新兴机制见解。我们探讨了这些原则，以突出基因调控中的生物学挑战，lncRNA 非常适合发挥仅由 DNA 元件或蛋白调节剂无法发挥的作用，例如在核内作为调节信号的空间放大器。
