The nonsense-mediated mRNA decay (NMD) pathway,
present in most eukaryotic cells, is a specialized
pathway that leads to the recognition and rapid
degradation of mRNAs with premature termination
codons and, importantly, some wild-type
mRNAs. Earlier studies demonstrated that aberrant
mRNAs with artificially extended 3’-untranslated
regions (3’-UTRs) are degraded by NMD. However,
the extent to which wild-type mRNAs with long
3’-UTRs are degraded by NMD is not known.
We used a global approach to identify wild-type
mRNAs in Saccharomyces cerevisiae that have
longer than expected 3’-UTRs, and of these
mRNAs tested, 91% were degraded by NMD. We
demonstrate for the first time that replacement of
the natural, long 3’-UTR from wild-type PGA1
mRNA, which encodes a protein that is important
for cell wall biosynthesis, with a short 3’-UTR renders
it immune to NMD. The natural PGA1 3’-UTR is
sufficient to target a NMD insensitive mRNA for
decay by the NMD pathway. Finally, we show that
nmd mutants are sensitive to Calcofluor White,
which suggests that the regulation of PGA1 and
other cell wall biosynthesis proteins by NMD is
physiologically significant
