Causes, Consequences and Challenges of Intron Retention in lncRNAs

Alternative splicing is a major player in post-transcriptional gene regulation leading to transcript variant and protein isoform diversity. Intron retention (IR) is a type of alternative splicing resulting in inclusion of sequences in mature RNA which can significantly affect RNA stability, localization, and function. Although IR has not been extensively investigated, emerging evidence suggests that it plays a crucial role in gene expression regulation. Compared to messenger RNAs (mRNAs) derived by protein coding genes, long non-coding RNAs (lncRNAs) show inefficient splicing, more diverse alternative splicing patterns, and higher rates of IR. However, the consequences of IR in lncRNA function are much less straightforward with several intrinsic challenges influencing this phenomenon. In this review, we summarize the causes and consequences of IR in lncRNAs, how they differ from mRNAs, the challenges that lie in studying IR in lncRNAs, and the necessary steps for further investigation.