The many faces of long noncoding RNAs

Abstract

Over the past few years, the field of noncoding RNAs has grown from a niche for geneticists into a prominent domain of mainstream biology. Advances in genomic technologies have provided a more comprehensive view of the mammalian genome, improving our knowledge of regions of the genome devoid of protein-coding potential. A large body of evidence supports the proposal that noncoding RNAs account for a large proportion of the transcriptional output of any given cell and tissue type. This review will delve into the biogenesis and function of long noncoding RNAs. We will discuss our current understanding of these molecules as major chromatin players, and explore future directions in the field.

Keywords: eRNAs; enhancer; lncRNAs; noncoding; transcription.

Figure 1. Mechanism of transcriptional activation mediated by enhancer RNAs

The model illustrates different regulatory steps that lead to the activation of a protein coding gene. A typical p300/CBP-dependent enhancer is located distal from its target protein coding locus (I) and depends on p300/CBP to sustain H3K27 acetylation and maintain an open chromatin state. Binding of a sequence specific transcription factor (II) recruits the Mediator complex (Med) to the enhancer, which engages the RNAPII machinery (III) to initiate transcription on both strands. The short-lived eRNA transcripts remain associated with chromatin and bind to Mediator/Cohesin to help enforce a DNA looping between the enhancer and the distal gene (IV). Such chromatin conformation changes culminate in the transcriptional activation of the target gene, resulting in the production of mature messenger RNAs that can be exported to the cytoplasm (IV).