Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae.

Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes' ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.