Eukaryotic genomes are pervasively transcribed, with tens of thousands of RNAs emanating from uni- and bi-directional promoters and from active enhancers. In vertebrates, thousands of loci in each species produce a class of transcripts called long noncoding RNAs (lncRNAs) that are typically expressed at low levels and do not appear to give rise to functional proteins. Substantial numbers of lncRNAs are expressed at specific stages of embryonic development, in many cases from regions flanking key developmental regulators. Here, the authors review the known biological functions of such lncRNAs and the emerging paradigms of their modes of action. They also provide an overview of the growing arsenal of methods for lncRNA identification, perturbation and functional characterization.
LncRNA modes of action
(A) For some lncRNA loci, the act of transcription itself plays a role in mediating the function of the lncRNA, for example by affecting the underlying chromatin structure of the locus. In this context, the RNA product itself and its sequence are inconsequential. (B) By contrast, other lncRNAs act in the vicinity of their site of transcription, recruiting or diverting specific factors, which may recognize the RNA in sequence-specific or nonspecific ways. (C) Other lncRNAs leave their site of transcription and act elsewhere, typically in a sequence- or structure-dependent manner, and via interactions with protein and other RNA factors.