Molecular mechanisms of long noncoding RNAs

Abstract

Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified.

Figure 1

Schematic diagram of the four archetypes of lncRNA mechanism. Archetype I: As Signals, lncRNA expression can faithfully reflect the combinatorial actions of transcription factors (colored ovals) or signaling pathways to indicate gene regulation in space and time. Archetype II: As Decoys, lncRNAs can titrate away transcription factors and other proteins away from chromatin, or titrate the protein factors into nuclear subdomains. A further example of decoys is lncRNA decoy for miRNA target sites (not shown on schematic). Archetype III: As Guides, lncRNAs can recruit chromatin modifying enzymes to target genes, either in cis (near the site of lncRNA production) or in trans to distant target genes. Archetype IV: As scaffolds, lncRNAs can bring together multiple proteins to form ribonucleoprotein complexes. The lncRNA-RNP may act on chromatin as illustrated to affect histone modifications. In other instances, the lncRNA scaffold is structural and stabilizes nuclear structures or signaling complexes