Functional classification and experimental dissection of long noncoding RNAs

Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bi-directional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. UT Southwestern researchers categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology with great potential to advance our understanding of normal physiology and disease.

Functions of lncRNA Loci in Local Gene Regulation

The ability of a lncRNA locus to regulate the expression of nearby genes in cis may be attributable to sequence-specific functions of the mature lncRNA transcript (A), may require transcription or splicing of an RNA, but the lncRNA itself is not functional (B), or may be due to DNA elements within the lncRNA promoter or gene body that function independently of the transcribed RNA (C). Pol II, RNA polymerase II; TF, transcription factor.