Long non-coding RNAs: modulators of nuclear structure and function

Abstract

Long non-coding (lnc)RNAs are emerging key factors in the regulation of various cellular processes. In the nucleus, these include the organization of nuclear sub-structures, the alteration of chromatin state, and the regulation of gene expression through the interaction with effector proteins and modulation of their activity. Collectively, lncRNAs form the core of attractive models explaining aspects of structural and dynamic regulation in the nucleus across time and space. Here we review recent studies that characterize the molecular function of a subset of these molecules in the regulation and fine-tuning of nuclear state.

Figure 1. Recent insight into the molecular functions of nuclear lncRNAs

Cell-state specific expression of individual lncRNAs can modulate the targeting of interacting proteins, their activity, or the structural composition of multi-protein complexes. A) Transcriptional regulation can occur in trans through the targeting of silencing (or activating, not pictured) chromatin-modifying complexes. Examples discussed in the main text include HOTAIR, Fendrr and Braveheart. B) LncRNAs can act as “decoys”, sequestering transcription repressors away from their cognate target gene promoters. Examples include Gas5, PANDA and Lethe. C) Transcriptional modulation of neighboring genes in cis involves lncRNA-mediated recruitment of chromatin factors (ANRIL and Mistral) and may involve lncRNA-dependent intra-chromosomal contact to gene promoters (HOTTIP and several lncRNAs with enhancer-like function [30,64]). D) Neat1 lncRNA serves to assemble and maintain paraspeckle nuclear bodies.