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Molecular and Cellular Biology, October 1999, p. 6710-6719, Vol. 19, No. 10
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 Transcriptomedagger

Michael J. Lelivelt and Michael R. Culbertson*

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.

* 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.

dagger Laboratory of Genetics paper 3529.

Molecular and Cellular Biology, October 1999, p. 6710-6719, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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