Papers in the Biological Sciences


Date of this Version



Nucleic Acids Research, 2009, Vol. 37, No. 9 2771–2778


Copyright 2009 The Author(s)


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.

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