title: Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins.
abstract: Selective translation of survival proteins is an important facet of the cellular stress response. We recently demonstrated that this translational control involves a stress-specific reprogramming of modified ribonucleosides in tRNA. Here we report the discovery of a step-wise translational control mechanism responsible for survival following oxidative stress. In yeast exposed to hydrogen peroxide, there is a Trm4 methyltransferase-dependent increase in the proportion of tRNA(Leu(CAA)) containing m(5)C at the wobble position, which causes selective translation of mRNA from genes enriched in the TTG codon. Of these genes, oxidative stress increases protein expression from the TTG-enriched ribosomal protein gene RPL22A, but not its unenriched paralogue. Loss of either TRM4 or RPL22A confers hypersensitivity to oxidative stress. Proteomic analysis reveals that oxidative stress causes a significant translational bias towards proteins coded by TTG-enriched genes. These results point to stress-induced reprogramming of tRNA modifications and consequential reprogramming of ribosomes in translational control of cell survival.
authors: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors: Clement T Y
authors: CT
authors: Chan
authors: Yan Ling Joy
authors: YL
authors: Pang
authors: Wenjun
authors: W
authors: Deng
authors: I Ramesh
authors: IR
authors: Babu
authors: Madhu
authors: M
authors: Dyavaiah
authors: Thomas J
authors: TJ
authors: Begley
authors: Peter C
authors: PC
authors: Dedon
mesh_terms: D003062:Codon / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D040901:Proteomics; D012343:RNA, Transfer / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012359:tRNA Methyltransferases / Q000235:genetics
chemical_list: D003062:Codon; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer; D006861:Hydrogen Peroxide; D012359:tRNA Methyltransferases; C024845:NCL1 protein, S cerevisiae