Originally published as Genetics Published Articles Ahead of Print on July 29, 2007.

Genetics, Vol. 177, 773-784, October 2007, Copyright © 2007
doi:10.1534/genetics.107.073205

A Genomic Screen in Yeast Reveals Novel Aspects of Nonstop mRNA Metabolism

Marenda A. Wilson, Stacie Meaux and Ambro van Hoof1

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030

1 Corresponding author: University of Texas Health Science Center, 6431 Fannin, MSB 1.212, Houston, TX 77030.
E-mail: ambro.van.hoof{at}uth.tmc.edu

Nonstop mRNA decay, a specific mRNA surveillance pathway, rapidly degrades transcripts that lack in-frame stop codons. The cytoplasmic exosome, a complex of 3'–5' exoribonucleases involved in RNA degradation and processing events, degrades nonstop transcripts. To further understand how nonstop mRNAs are recognized and degraded, we performed a genomewide screen for nonessential genes that are required for nonstop mRNA decay. We identified 16 genes that affect the expression of two different nonstop reporters. Most of these genes affected the stability of a nonstop mRNA reporter. Additionally, three mutations that affected nonstop gene expression without stabilizing nonstop mRNA levels implicated the proteasome. This finding not only suggested that the proteasome may degrade proteins encoded by nonstop mRNAs, but also supported previous observations that rapid decay of nonstop mRNAs cannot fully explain the lack of the encoded proteins. Further, we show that the proteasome and Ski7p affected expression of nonstop reporter genes independently of each other. In addition, our results implicate inositol 1,3,4,5,6-pentakisphosphate as an inhibitor of nonstop mRNA decay.