(A) NMD substrates typically have short open reading frames (ORFs) followed by long 3’ untranslated regions (3’ UTRs; top). Some NMD substrates also have an annotated ORF (middle). Short ORFs followed by relatively long 3'UTRs are also randomly present in incorrectly spliced mRNA transcripts (bottom). (B) Three examples of phenotypic traits observed in the absence of NMD; each trait is mediated by the stabilization of the mRNA shown in the second column. The first two links were observed in yeast (Johansson and Jacobson, 2010; Addinall et al., 2011); the last was observed by Nelson et al. in flies.