Beyond RNA Modification: A Novel Role for tRNA modifying Enzyme in Oxidative Stress Response

ABSTRACT: RNA modifications are fundamental to regulating essential cellular processes, including RNA folding, stability, gene expression, and the accuracy and efficiency of decoding. These modifications are added post-transcriptionally by specialized enzymes, yet their broader roles beyond RNA modification remain poorly understood. In this study, we uncovered a novel function for Vibrio cholerae tRNA dihydrouridine synthase B (VcDusB) in bacterial adaptation to oxidative stress. While VcDusB is traditionally recognized for catalyzing the reduction of uridine to dihydrouridine in tRNA, our findings revealed that its deletion severely compromises V. cholerae survival under hydrogen peroxide-induced oxidative stress. Unexpectedly, VcDusB not only modulated codon decoding efficiency at its target tRNAs, but also influenced global translation, including codons unrelated to its canonical substrates—a phenomenon particularly evident under oxidative stress conditions. Proteomic analysis of the ∆dusB strain exposed a substantial reduction in protein synthesis, highlighting a widespread translational defect in response to stress. Strikingly, point mutations in DusB demonstrated that its protective role during stress was independent of its tRNA modification activity. Instead, its ability to bind tRNA and its NADPH oxidase activity proved vital for survival. These findings reveal a previously unrecognized, non-canonical function of DusB in oxidative stress defense, expanding our understanding of RNA-modifying enzymes. More broadly, this work paves the way for investigating the multifaceted roles of these enzymes in cellular metabolism and stress responses, far beyond their established functions in RNA modification

INSTRUMENT(S):

ORGANISM(S): Vibrio Cholerae O1 Biovar El Tor

SUBMITTER: Magalie Duchateau  

LAB HEAD: Zeynep BAHAROGLU

PROVIDER: PXD057145 | Pride | 2025-12-22

REPOSITORIES: Pride