Long noncoding RNAs: an emerging link between gene regulation and nuclear organization

•Many nuclear-retained long noncoding RNAs (lncRNAs) can recruit chromatin regulatory proteins to genomic DNA to regulate gene expression.•Several of these lncRNAs can search for regulatory targets by exploiting the 3D conformation of the nucleus.•Several lncRNAs are essential for the establishment and maintenance of 3D nuclear domains.•The role of lncRNAs in regulating gene expression and shaping nuclear organization may occur through some shared molecular mechanisms.

Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs) that play important roles in diverse biological processes. As a class, lncRNAs are generally enriched in the nucleus and, specifically, within the chromatin-associated fraction. Consistent with their localization, many lncRNAs have been implicated in the regulation of gene expression and in shaping 3D nuclear organization. In this review, we discuss the evidence that many nuclear-retained lncRNAs can interact with various chromatin regulatory proteins and recruit them to specific sites on DNA to regulate gene expression. Furthermore, we discuss the role of specific lncRNAs in shaping nuclear organization and their emerging mechanisms. Based on these examples, we propose a model that explains how lncRNAs may shape aspects of nuclear organization to regulate gene expression.