Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome - PubMed (original) (raw)

Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome

M J Lelivelt et al. Mol Cell Biol. 1999 Oct.

Abstract

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.

PubMed Disclaimer

Figures

FIG. 1

Box plots representing the distribution of upf IKI scores. The box delineates the interquartile region between the 25th and 75th percentiles. Whiskers delineate the 10th and 90th percentiles. Values lying outside this region are displayed as circles. Each circle represents IKI scores for multiple mRNAs that happen to fall at the same position.

FIG. 2

Distribution of all CKI scores across 6,421 mRNAs analyzed by HDOA. A score of −1.0 indicates a _UPF_-dependent decrease in every trial for every _upf_− strain; a score of +1.0 indicates a _UPF_-dependent increase in every trial for every _upf_− strain; a score of zero represents no average change.

References

1. Applequist S E, Selg M, Raman C, Jack H M. Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein. Nucleic Acids Res. 1997;25:814–821. - PMC - PubMed
1. Arima K, Oshima T, Kubota I, Nakamura N, Mizunaga T, Toh-e A. The nucleotide sequence of the yeast PHO5 gene: a putative precursor of repressible acid phosphatase contains a signal peptide. Nucleic Acids Res. 1983;11:1657–1672. - PMC - PubMed
1. Atkin A L, Schenkman L R, Eastham M, Dahlseid J N, Lelivelt M J, Culbertson M R. Relationship between yeast polyribosomes and Upf proteins required for nonsense mRNA decay. J Biol Chem. 1997;272:22163–22172. - PubMed
1. Badcock, K., C. M. Churcher, B. G. Barrell, M. A. Rajandream, and S. V. Walsh. 1997. Swiss-Prot accession no. , gene name SPAC16C9.06C.
1. Bun-Ya M, Nishimura M, Harashima S, Oshima Y. The PHO84 gene of Saccharomyces cerevisiae encodes an inorganic phosphate transporter. Mol Cell Biol. 1991;11:3229–3238. - PMC - PubMed

Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome - PubMed (original) (raw)