Regulation of gene expression by cis-acting long non-coding RNAs

Long non-coding RNAs (lncRNAs) are diverse transcription products emanating from thousands of loci in mammalian genomes. Cis-acting lncRNAs, which constitute a substantial fraction of lncRNAs with an attributed function, regulate gene expression in a manner dependent on the location of their own sites of transcription, at varying distances from their targets in the linear genome. Through various mechanisms, cis-acting lncRNAs have been demonstrated to activate, repress or otherwise modulate the expression of target genes. We discuss the activities that have been ascribed to cis-acting lncRNAs, the evidence and hypotheses regarding their modes of action, and the methodological advances that enable their identification and characterization. The emerging principles highlight lncRNAs as transcriptional units highly adept at contributing to gene regulatory networks and to the generation of fine-tuned spatial and temporal gene expression programmes. Recent methodological advances have driven the identification and characterization of cis-acting long non-coding RNAs (lncRNAs), which modulate target gene expression through various mechanisms and operate at various genomic distances. This Review discusses recent insights into the evolution and functions of these cis-acting lncRNAs.