Intron retention (IR), a well‐conserved form of alternative splicing, is widespread among eukaryotic organisms. It serves as an orchestrated program for regulating gene expression. A previously reported role of IR is to induce intron‐retained transcript (IRT) degradation via the nonsense‐mediated mRNA decay (NMD) pathway, resulting in the downregulation of gene expression. However, accumulating evidence indicates that most IRTs are detained in the nucleus, and thus, IR can downregulate gene expression through the storage of IRTs in the nucleus. (...) Although the importance of IRTs in gene expression regulation is well established, the detailed mechanisms remain unclear. Here, we propose a potential model to explain how IRTs are retained in the nucleus and respond to environmental changes or developmental transitions. Plenty of future studies are still ahead of us to fully dissect the biological function of IR and the underlying mechanisms. (shrink)

The explosion in sequencing technologies has provided us with an instrument to describe mammalian transcriptomes at unprecedented depths. This has revealed that alternative splicing is used extensively not only to generate protein diversity, but also as a means to regulate gene expression post‐transcriptionally. Intron retention (IR) is overwhelmingly perceived as an aberrant splicing event with little or no functional consequence. However, recent work has now shown that IR is used to regulate a specific differentiation event within the haematopoietic (...) system by coupling it to nonsense‐mediated mRNA decay (NMD). Here, we highlight how IR and, more broadly, alternative splicing coupled to NMD (AS‐NMD) can be used to regulate gene expression and how this is deregulated in disease. We suggest that the importance of AS‐NMD is not restricted to the haematopoietic system but that it plays a prominent role in other normal and aberrant biological settings. (shrink)