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

M J Lelivelt1, M R Culbertson

  • 1Laboratories of Genetics and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706, USA.

Molecular and Cellular Biology
|September 22, 1999
PubMed

Insights

The Upf proteins regulate mRNA levels beyond their role in nonsense-mediated mRNA decay (NMD). Loss of UPF genes alters the abundance of hundreds of mRNAs, impacting gene expression in yeast.

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Gene Expression Regulation

Background:

  • RNA surveillance mechanisms, including nonsense-mediated mRNA decay (NMD), prevent the production of truncated proteins.
  • The UPF1, UPF2, and UPF3 proteins are essential components of NMD pathways in eukaryotes, including Saccharomyces cerevisiae.
  • Previous studies established the role of UPF proteins in RNA surveillance and mRNA quality control.

Purpose of the Study:

  • To investigate the broader role of UPF proteins in regulating mRNA accumulation beyond NMD.
  • To identify global changes in the yeast transcriptome resulting from the loss of UPF gene function.
  • To understand how UPF proteins control the abundance of a large set of mRNAs.

Main Methods:

  • Utilized high-density oligonucleotide arrays to perform a genome-wide transcriptome analysis in yeast.
  • Generated null mutations in UPF1, UPF2, and UPF3 genes to assess the impact on mRNA levels.
  • Analyzed changes in mRNA abundance and distribution across different functional categories.

Main Results:

  • Loss of UPF gene function led to altered accumulation of hundreds of mRNAs, with most increasing and some decreasing in abundance.
  • The affected mRNAs were consistent across mutations in any of the three UPF genes.
  • UPF-dependent mRNAs were underrepresented in protein synthesis and protein destination categories and were generally less abundant than average mRNAs.

Conclusions:

  • UPF proteins play a significant role in controlling the overall abundance of a large number of mRNAs, in addition to their established function in NMD.
  • The findings suggest that UPF proteins may regulate the expression of highly abundant mRNAs.
  • A model is proposed to explain how Upf proteins might control mRNA abundance across the transcriptome.

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