Beyond RNA modification: a novel role for tRNA modifying enzyme in oxidative stress response and metabolism

RNA modifications play a fundamental role in regulating essential cellular processes, including translation fidelity and stress adaptation. While these modifications are installed post-transcriptionally by specialized enzymes, their broader functional roles remain largely unexplored. Here, we uncover an unexpected function for the Vibrio cholerae tRNA dihydrouridine synthase B (VcDusB) beyond its canonical role in tRNA dihydrouridylation. We show that deletion of dusB severely compromises V. cholerae resistance to oxidative stress, not through the loss of tRNA modification, but via disruption of an intrinsic NADPH oxidase activity. Mutational analyses reveal that DusB redox function is essential for survival under oxidative stress. Proteomic and transposon insertion sequencing analysis further linked DusB to NADPH homeostasis and metabolic reprogramming during stress adaptation. These findings redefine DusB as a bifunctional enzyme coupling tRNA modification to redox regulation, expanding the functional repertoire of RNA-modifying enzymes in stress adaptation. More broadly, this work paves the way for exploring the evolutionary versatility of tRNA-modifying enzymes, suggesting that their functions extend far beyond RNA metabolism to direct integration of translational control with cellular redox state.

Authors

Institutions

Publication Details

Journal
Nucleic Acids Research
Published
2025-10-29
DOI
https://doi.org/10.1093/nar/gkaf1276
Citations
1
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.81

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Beyond RNA modification: a novel role for tRNA modifying enzyme in oxidative stress response and metabolism

Quentin Giai‐Gianetto, Louna Fruchard, Zeynep Baharoglu, Caroline Rouard et al.
1 citations
Nucleic Acids Research
RNA modifications and cancer
0.81
article

Beyond RNA modification: a novel role for tRNA modifying enzyme in oxidative stress response and metabolism

Quentin Giai‐Gianetto, Louna Fruchard, Zeynep Baharoglu, Caroline Rouard, Mariette Matondo, Claudia Sudol, Quentin Thuillier, Virginie Marchand, Magalie Duchateau, Frédéric Bonhomme, Julia Bos, Damien Brégeon, Didier Mazel, Djemel Hamdane, Yuri Motorin, Léo Hardy, Aurore Treffkorn-Maurau
article en
1 citations

Abstract

RNA modifications play a fundamental role in regulating essential cellular processes, including translation fidelity and stress adaptation. While these modifications are installed post-transcriptionally by specialized enzymes, their broader functional roles remain largely unexplored. Here, we uncover an unexpected function for the Vibrio cholerae tRNA dihydrouridine synthase B (VcDusB) beyond its canonical role in tRNA dihydrouridylation. We show that deletion of dusB severely compromises V. cholerae resistance to oxidative stress, not through the loss of tRNA modification, but via disruption of an intrinsic NADPH oxidase activity. Mutational analyses reveal that DusB redox function is essential for survival under oxidative stress. Proteomic and transposon insertion sequencing analysis further linked DusB to NADPH homeostasis and metabolic reprogramming during stress adaptation. These findings redefine DusB as a bifunctional enzyme coupling tRNA modification to redox regulation, expanding the functional repertoire of RNA-modifying enzymes in stress adaptation. More broadly, this work paves the way for exploring the evolutionary versatility of tRNA-modifying enzymes, suggesting that their functions extend far beyond RNA metabolism to direct integration of translational control with cellular redox state.

Nucleic Acids ResearchVol. 53(22)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Institut Pasteur (FR), Université Sorbonne Nouvelle (FR), Université Paris Cité (FR), Sorbonne Université (FR), Institut de Biologie Paris-Seine (FR), Epigénétique et Destin Cellulaire (FR), Ingénierie Moléculaire et Physiopathologie Articulaire (FR), Expression Génétique Microbienne (FR), Développement Adaptation et Vieillissement (FR), Université Paris 1 Panthéon-Sorbonne (FR), Université de Lorraine (FR)
Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique
Openalex Percentile: Top 21%
RNA modifications and cancer
0.81
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.