A functional connection between translation elongation and protein folding at the ribosome exit tunnel in Saccharomyces cerevisiae
Proteostasis is a fundamental network of cellular pathways that ensures the optimal concentration and composition of correctly folded proteins within cells in normal and stress conditions. Among key components of this network are the molecular chaperones, which mediate protein folding but also act as modulators of protein synthesis. We have reported on a functional link between translation and de novo folding of proteins in the yeast Saccharomyces cerevisiae by uncovering a specific synthetic-lethal interaction between apparent unrelated mutant variants, the uL3[W255C] variant of the ribosomal protein uL3 and the null mutants of Zuo1 and Ssz1. Zuo1 and Ssz1 are components of the chaperone system named as ribosome-associated complex. Here, we performed a genome-wide analysis of ribosome dynamics by 5PSeq (Pelechano et al. 2015 PMID 2604644) in strains harbouring either wild-type uL3 or mutant uL3[W255C] in the presence or absence of Zuo1 or Ssz1. This method allows the study of ribosome dynamics, by sequencing 5' phosphorylated mRNA co-translational degradation intermediates. Our results indicate that the rpl3[W255C] mutant is slightly impaired in translation elongation, defect that is significantly enhanced when combined with the deprivation of either Zuo1 or Ssz1. Overall design: HT-5Pseq was performed with 3 replicates each for 6 strains of S. cerevisiae.