Intron retention is a common form of alternative splicing in plants and unicellular eukaryotes; however, its prevalence in mammals was unclear. Braunschweig et al. carried out high-throughput RNA sequencing from ∼40 human and mouse cell types and found evidence for intron retention in transcripts from up to 75% of genes. In addition, they identified sequence features in the mRNAs that control intron retention. With this approach the team showed that intron retention seems to be a mechanism to minimize the expression of tissue-inappropriate genes; for example, stop codons in the retained introns result in premature translational termination and nonsense-mediated mRNA decay.