Gene set coregulated by the Saccharomyces cerevisiae nonsense-mediated mRNA decay pathway

Rachel Taylor, Bessie Wanja Kebaara, Tara Nazarenus, Ashley Jones, Rena Yamanaka, Rachel Uhrenholdt, Jason P. Wendler, Audrey L. Atkin

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The nonsense-mediated mRNA decay (NMD) pathway has historically been thought of as an RNA surveillance system that degrades mRNAs with premature translation termination codons, but the NMD pathway of Saccharomyces cerevisiae has a second role regulating the decay of some wild-type mRNAs. In S. cerevisiae, a significant number of wild-type mRNAs are affected when NMD is inactivated. These mRNAs are either wild-type NMD substrates or mRNAs whose abundance increases as an indirect consequence of NMD. A current challenge is to sort the mRNAs that accumulate when NMD is inactivated into direct and indirect targets. We have developed a bioinformatics-based approach to address this challenge. Our approach involves using existing genomic and function databases to identify transcription factors whose mRNAs are elevated in NMD-deficient cells and the genes that they regulate. Using this strategy, we have investigated a coregulated set of genes. We have shown that NMD regulates accumulation of ADR1 and GAL4 mRNAs, which encode transcription activators, and that Adr1 is probably a transcription activator of ATS1. This regulation is physiologically significant because overexpression of ADR1 causes a respiratory defect that mimics the defect seen in strains with an inactive NMD pathway. This strategy is significant because it allows us to classify the genes regulated by NMD into functionally related sets, an important step toward understanding the role NMD plays in the normal functioning of yeast cells.

Original languageEnglish (US)
Pages (from-to)2066-2077
Number of pages12
JournalEukaryotic Cell
Volume4
Issue number12
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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