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Nat Rev Mol Cell Biol. 2016 Dec;17(12):756-770. doi: 10.1038/nrm.2016.126. Epub 2016 Oct 26.

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression.

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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.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.


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.

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