Nonsense-mediated decay (NMD), also called mRNA surveillance, is an 
evolutionarily conserved pathway that degrades mRNAs that prematurely terminate 
translation. To date, the pathway in mammalian cells has been shown to depend on 
the presence of a cis-acting destabilizing element that usually consists of an 
exon-exon junction generated by the process of pre-mRNA splicing. Whether or not 
mRNAs that derive from naturally intronless genes, that is, mRNAs not formed by 
the process of splicing, are also subject to NMD has yet to be investigated. The 
possibility of NMD is certainly reasonable considering that mRNAs of 
Saccharomyces cerevisiae are subject to NMD even though most derive from 
naturally intronless genes. In fact, mRNAs of S. cerevisiae generally harbor a 
loosely defined splicing-independent destabilizing element that has been 
proposed to function in NMD analogously to the spliced exon-exon junction of 
mammalian mRNAs. Here, we demonstrate that nonsense codons introduced into 
naturally intronless genes encoding mouse heat shock protein 70 or human histone 
H4 fail to elicit NMD. Failure is most likely because each mRNA lacks a 
cis-acting destabilizing element, because insertion of a spliceable intron a 
sufficient distance downstream of a nonsense codon within either gene is 
sufficient to elicit NMD.