Nuclear mechanisms of gene expression control: pre-mRNA splicing as a life or death decision

Thousands of genes produce polyadenylated mRNAs that still contain one or more introns. These transcripts are known as retained intron RNAs (RI-RNAs). In the past 10 years, RI-RNAs have been linked to post-transcriptional alternative splicing in a variety of developmental contexts, but they can also be dead-end products fated for RNA decay. Here we discuss the role of intron retention in shaping gene expression programs, as well as recent evidence suggesting that the biogenesis and fate of RI-RNAs is regulated by nuclear organization. We discuss the possibility that proximity of RNA to nuclear speckles - biomolecular condensates that are highly enriched in splicing factors and other RNA binding proteins - is associated with choices ranging from efficient co-transcriptional splicing, export and stability to regulated post-transcriptional splicing and possible vulnerability to decay.