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Molecular and Cellular Biology, October 1999, p. 6710-6719, Vol. 19, No. 10
Laboratories of Genetics and Molecular
Biology, University of Wisconsin, Madison, Wisconsin 53706
Received 5 March 1999/Returned for modification 10 May
1999/Accepted 16 June 1999
mRNAs are monitored for errors in gene expression by RNA
surveillance, in which mRNAs that cannot be fully translated are degraded by the nonsense-mediated mRNA decay pathway (NMD). RNA surveillance ensures that potentially deleterious truncated proteins are seldom made. NMD pathways that promote surveillance have been found
in a wide range of eukaryotes. In Saccharomyces cerevisiae, the proteins encoded by the UPF1, UPF2, and
UPF3 genes catalyze steps in NMD and are required for RNA
surveillance. In this report, we show that the Upf proteins are also
required to control the total accumulation of a large number of mRNAs
in addition to their role in RNA surveillance. High-density
oligonucleotide arrays were used to monitor global changes in the yeast
transcriptome caused by loss of UPF gene function. Null
mutations in the UPF genes caused altered accumulation of
hundreds of mRNAs. The majority were increased in abundance, but some
were decreased. The same mRNAs were affected regardless of which of the
three UPF gene was inactivated. The proteins encoded by
UPF-dependent mRNAs were broadly distributed by function
but were underrepresented in two MIPS (Munich Information Center for
Protein Sequences) categories: protein synthesis and protein
destination. In a UPF+ strain, the average
level of expression of UPF-dependent mRNAs was threefold
lower than the average level of expression of all mRNAs in the
transcriptome, suggesting that highly abundant mRNAs were
underrepresented. We suggest a model for how the abundance of hundreds
of mRNAs might be controlled by the Upf proteins.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Yeast Upf Proteins Required for RNA Surveillance
Affect Global Expression of the Yeast Transcriptome
*
Corresponding author. Mailing address: University of
Wisconsin, Laboratory of Molecular Biology, 435A Bock Laboratories,
1525 Linden Dr., Madison, WI 53706. Phone: (608) 262-5388. Fax: (608) 262-4570. E-mail: mrculber{at}facstaff.wisc.edu.
Laboratory of Genetics paper 3529.
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