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Vol. 20, Issue 8, 2229-2241, April 15, 2009

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Mutants of the Paf1 Complex Alter Phenotypic Expression of the Yeast Prion [PSI+]

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110

Submitted August 7, 2008; Revised February 10, 2009; Accepted February 11, 2009
Monitoring Editor: Jonathan S. Weissman

The yeast [PSI+] prion is an epigenetic modifier of translation termination fidelity that causes nonsense suppression. The prion [PSI+] forms when the translation termination factor Sup35p adopts a self-propagating conformation. The presence of the [PSI+] prion modulates survivability in a variety of growth conditions. Nonsense suppression is essential for many [PSI+]-mediated phenotypes, but many do not appear to be due to read-through of a single stop codon, but instead are multigenic traits. We hypothesized that other global mechanisms act in concert with [PSI+] to influence [PSI+]-mediated phenotypes. We have identified one such global regulator, the Paf1 complex (Paf1C). Paf1C is conserved in eukaryotes and has been implicated in several aspects of transcriptional and posttranscriptional regulation. Mutations in Ctr9p and other Paf1C components reduced [PSI+]-mediated nonsense suppression. The CTR9 deletion also alters nonsense suppression afforded by other genetic mutations but not always to the same extent as the effects on [PSI+]-mediated read-through. Our data suggest that the Paf1 complex influences mRNA translatability but not solely through changes in transcript stability or abundance. Finally, we demonstrate that the CTR9 deletion alters several [PSI+]-dependent phenotypes. This provides one example of how [PSI+] and genetic modifiers can interact to uncover and regulate phenotypic variability.

Address correspondence to: Heather L. True (htrue{at}cellbiology.wustl.edu)

Abbreviations used: , null; GdnHCl, guanidine hydrochloride; GFP, green fluorescent protein; NM, prion-forming domain of Sup35p; Paf1C, Paf1 complex; SD, synthetic dropout; s[PSI+], strong [PSI+]; SDD-AGE, semi-denaturing detergent agarose gel electrophoresis; w[PSI+], weak [PSI+]; WT, wild-type; YPD, yeast extract, peptone, and dextrose.