Reprogramming of tRnA modifications controlsthe oxidative stress response by codon-biasedtranslation of proteins

摘要

Selective translation of survival proteins is an important facet of the cellular stressresponse. We recently demonstrated that this translational control involves a stress-specificreprogramming of modified ribonucleosides in tRnA. Here we report the discovery of a stepwise translational control mechanism responsible for survival following oxidative stress.In yeast exposed to hydrogen peroxide, there is a Trm4 methyltransferase-dependent increasein the proportion of tRnALeu(CAA)containing m5C at the wobble position, which causes selectivetranslation of mRnA from genes enriched in the TTG codon. of these genes, oxidative stressincreases protein expression from the TTG-enriched ribosomal protein gene RPL22A, but notits unenriched paralogue. Loss of either TRM4 or RPL22A confers hypersensitivity to oxidativestress. Proteomic analysis reveals that oxidative stress causes a significant translationalbias towards proteins coded by TTG-enriched genes. These results point to stress-inducedreprogramming of tRnA modifications and consequential reprogramming of ribosomes intranslational control of cell survival.