MKT1alleles regulate stress responses through post-transcriptional modulation of Puf3 targets in budding yeast

ABSTRACT MKT1 is a pleiotropic stress response gene identified by several quantitative trait studies with MKT1 89G as a causal variant, contributing to growth advantage in multiple stress environments. MKT1 has been shown to regulate HO endonuclease post-transcriptionally via the Pbp1-Pab1 complex. RNA-binding protein Puf3 modulates a set of nuclear-encoded mitochondrial transcripts whose expression was found to be affected by MKT1 alleles. This study attempts to relate the MKT1 allele-derived growth advantage with the stability of Puf3 targets during stress and elucidate the roles of Pbp1 and Puf3 in this mechanism. Our results showed that the growth advantage of the MKT1 89G allele in cycloheximide and H O was PBP1 -dependent, whereas in 4NQO, the growth advantage was dependent on both PUF3 and PBP1 . We compared the mRNA decay kinetics of a set of Puf3 targets in multiple stress environments to understand the allele-specific regulation by MKT1 . In oxidative stress, the MKT1 89G allele modulated the differential expression of nuclear-encoded mitochondrial genes in a PBP1 and PUF3 -dependent manner. Additionally, MKT1 89G stabilised Puf3 targets, namely, COX17 , MRS1 , and RDL2, in an allele and stress-specific manner. Our results showed that COX17, MRS1, and RDL2 had a stress-specific response in stress environments, with the MKT1 89G allele contributing to better growth; this response was both PBP1 and PUF3 -dependent. Our results indicate that the common allele, MKT1 89G , regulates stress responses by differentially stabilising Puf3-target mitochondrial genes, which allows for the strain’s better growth in stress environments. TAKE AWAY MKT1 alleles vary stress responses by post-transcriptional modulation of Puf3 targets. PBP1 and PUF3 influence the regulation of Puf3 target stability under stress. Nuclear-encoded mitochondrial Puf3 targets COX17, MRS1 and RDL2, contribute to the growth advantage of MKT1 89G allele in oxidative stress.