Intron retention in mRNA: No longer nonsense: Known and putative roles of intron retention in normal and disease biology

Abstract

Until recently, retention of introns in mature mRNAs has been regarded as a consequence of mis-splicing. Intron-retaining transcripts are thought to be non-functional because they are readily degraded by nonsense-mediated decay. However, recent advances in next-generation sequencing technologies have enabled the detection of numerous transcripts that retain introns. As we review herein, intron-retaining mRNAs play an essential conserved role in normal physiology and an emergent role in diverse diseases. Intron retention should no longer be overlooked as a key mechanism that independently reduces gene expression in normal biology. Exploring its contribution to the development and/or maintenance of diseases is of increasing importance. Intron retention was once thought to be a consequence of mis-splicing but it is now established as an important mechanism controlling gene expression within the cell. Here, we review known functions of intron-retaining mRNAs in normal physiology, their role in disease, and explore potential novel cell functions for intron-retaining mRNAs.