Exploiting Natural Variation to Understand the Role of Mkt1p in Post-Transcriptional Gene Regulation
Authors: Crystal Crook 1,2; Emma Cox 1; Jeffrey Lewis 1
Affiliations: 1) University of Arkansas, Department of Biological Sciences; 2) University of Arkansas, Cell and Molecular Biology
Keywords: Comparative genomics & genome evolution
All organisms experience stress and have thus evolved sophisticated regulatory programs to coordinate stress defense. While traditionally research has focused on transcriptional responses to stress, substantial evidence suggests that cells also possess well-coordinated post-transcriptional responses. We have been taking advantage of natural variation in the Saccharomyces cerevisiae ethanol response to understand mechanisms underlying post-transcriptional stress defense, using the protein Mkt1p as a case study. Mutations in MKT1 are pleiotropic, affecting a number of traits including various stress tolerances. Additionally, we previously found that a polymorphism in MKT1 was responsible for a large number (>500) of differences in ethanol-responsive gene expression between laboratory and wild yeast strains. Because Mkt1p shares homology with RNA-binding proteins instead of transcription factors, and co-localizes with cytoplasmic processing (P) bodies known to regulate translation during stress in a strain dependent manner, we hypothesize that Mkt1p is a global post-transcriptional regulator. We have been employing proteomics and RNA immunoprecipitation in laboratory and wild yeast to better understand how Mkt1p may regulate expression post-transcriptionally during stress. We have found that sequence variation in Mkt1p results in large differences in protein interaction partners in wild versus laboratory yeast strains, thus offering a potential explanation for the dramatic pleiotropic effects of the MKT1 polymorphism.