Mutants of the Paf1 complex alter phenotypic expression of the yeast prion [PSI+].

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.
Mesh Terms:
Alleles, Cell Cycle Proteins, Codon, Nonsense, Gene Deletion, Gene Expression Regulation, Fungal, Genes, Recessive, Genetic Complementation Test, Multiprotein Complexes, Mutation, Nuclear Proteins, Peptide Termination Factors, Phenotype, Prions, Protein Biosynthesis, Protein Structure, Quaternary, RNA Processing, Post-Transcriptional, RNA, Messenger, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Suppression, Genetic, TATA-Box Binding Protein, Transcriptional Elongation Factors
Mol. Biol. Cell
Date: Apr. 01, 2009
Download Curated Data For This Publication
94618
Switch View:
  • Interactions 4