Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs

Abstract

The recent discovery that the human and other mammalian genomes produce thousands of long non-coding RNAs (lncRNAs) raises many fascinating questions. These mRNA-like molecules, which lack significant protein-coding capacity, have been implicated in a wide range of biological functions through diverse and as yet poorly understood molecular mechanisms. Despite some recent insights into how lncRNAs function in such diverse cellular processes as regulation of gene expression and assembly of cellular structures, by and large, the key questions regarding lncRNA mechanisms remain to be answered. In this review, we discuss recent advances in understanding the biology of lncRNAs and propose avenues of investigation that may lead to fundamental new insights into their functions and mechanisms of action. Finally, as numerous lncRNAs are dysregulated in human diseases and disorders, we also discuss potential roles for these molecules in human health.

Figure 1.

LncRNAs fall into one of three categories. (A) Long intervening non-coding RNAs (lincRNAs) are transcribed from regions far away from protein-coding genes. (B) Natural Antisense Transcripts (NATs) are transcribed from the opposite strand of a protein-coding gene. (C) Intronic lncRNAs (shown in green) are transcribed from within introns of protein-coding genes.

Figure 2.

LncRNAs exert their effects by diverse mechanisms. (A) lncRNAs can act as guides and tethers for chromatin-modifying complexes, and thus contribute to tissue-specific gene expression. (B) lncRNAs can act as molecular scaffolds for protein complexes that lack protein–protein interaction domains. (C) lncRNAs can bind to transcription factors and prevent them from binding to their target DNA sequence. (D) lncRNAs can interact directly with microRNAs (miRNAs) and prevent them from binding to mRNA, thus regulating protein synthesis.