The yeast metabolic cycle and oxidative RNA damage
The yeast metabolic cycle (YMC) in Saccharomyces cerevisiae provides a tractable cellular framework for investigating how mitochondrial redox state, antioxidant buffering, and biological timing shape transcriptome fidelity. We analyzed ribosomal-RNA-depleted whole-cell RNA sequencing (WRS) and RNA-seq-derived mismatch patterns across Low DO/high-respiration and High DO/lower-respiration phases. Here, we analyzed ribosomal-RNA-depleted whole-cell RNA sequencing (WRS) and RNA-seq-derived mismatch patterns across Low DO/high-respiration and High DO/lower-respiration phases. WRS identified statistically significant phase-differentially expressed genes, including Low DO-enriched and High DO-enriched genes at |log2FC| > 1. Low DO-enriched genes were dominated by ribosome biogenesis, rRNA processing, cytoplasmic translation, ribosomal subunit assembly, sulfur metabolism, and protein synthesis programs, whereas High DO-enriched genes were enriched for antioxidant defense, detoxification, oxidoreductase activity, and energy-generating pathways. We next quantified mismatch rate (MR) using a beta-binomial generalized linear mixed model (GLMM) and found a substitution-class-dependent, Low DO-associated mismatch response in Low DO relative to High DO. C>T, equivalent to G>A in pyrimidine-collapsed SBS notation, showed the strongest Low DO-associated increase at the mismatch level (FC = 1.074). Variant-rate analysis using a negative binomial GLMM also identified a significant Low DO-associated increase in C>T variants, together with larger relative increases in T>C and T>A. Recurrence analysis showed that most called variants were sample-specific, with only C>T showing a statistically supported High DO-Low DO distributional shift after correction. These findings indicate that Low DO/high-respiration is associated with a broader RNA-seq mismatch landscape rather than an exclusively C>T-specific response. The YMC therefore provides a useful eukaryotic model for studying how redox timing, antioxidant buffering, RNA processing, and transcriptome fidelity intersect in cellular resilience, with relevance to circadian disruption, sleep-wake instability, and human health.
The yeast metabolic cycle (YMC) in Saccharomyces cerevisiae provides a tractable cellular framework for investigating how mitochondrial redox state, antioxidant buffering, and biological timing shape transcriptome fidelity. We analyzed ribosomal-RNA-depleted whole-cell RNA sequencing (WRS) and RNA-seq-derived mismatch patterns across Low DO/high-respiration and High DO/lower-respiration phases. Here, we analyzed ribosomal-RNA-depleted whole-cell RNA sequencing (WRS) and RNA-seq-derived mismatch patterns across Low DO/high-respiration and High DO/lower-respiration phases. WRS identified statistically significant phase-differentially expressed genes, including Low DO-enriched and High DO-enriched genes at |log2FC| > 1. Low DO-enriched genes were dominated by ribosome biogenesis, rRNA processing, cytoplasmic translation, ribosomal subunit assembly, sulfur metabolism, and protein synthesis programs, whereas High DO-enriched genes were enriched for antioxidant defense, detoxification, oxidoreductase activity, and energy-generating pathways. We next quantified mismatch rate (MR) using a beta-binomial generalized linear mixed model (GLMM) and found a substitution-class-dependent, Low DO-associated mismatch response in Low DO relative to High DO. C>T, equivalent to G>A in pyrimidine-collapsed SBS notation, showed the strongest Low DO-associated increase at the mismatch level (FC = 1.074). Variant-rate analysis using a negative binomial GLMM also identified a significant Low DO-associated increase in C>T variants, together with larger relative increases in T>C and T>A. Recurrence analysis showed that most called variants were sample-specific, with only C>T showing a statistically supported High DO-Low DO distributional shift after correction. These findings indicate that Low DO/high-respiration is associated with a broader RNA-seq mismatch landscape rather than an exclusively C>T-specific response. The YMC therefore provides a useful eukaryotic model for studying how redox timing, antioxidant buffering, RNA processing, and transcriptome fidelity intersect in cellular resilience, with relevance to circadian disruption, sleep-wake instability, and human health.
Biomedical Research Center of the SAS