Adaptive cellular responses to ribosomal protein loss highlights SKN-1 dependent enhanced oxidative stress resistance. (A) Investigation of significantly differentially expressed genes at the RNA level across all haploinsufficient RP mutants, with a focus on significant gene ontology (GO) enrichments are shown. Log₂ fold-change gene expression estimates of representative GO categories that were enriched for overexpression (top) and underexpression (bottom) were plotted. All significantly enriched GO categories are provided in Table S3. The y-axis displays predicted RNA-seq log₂ fold change estimate distribution for each GO category as predicted by edgeR. GO categories are annotated on the side, where “N” denotes the number of differentially expressed genes within a category, and “X” represents the total number of genes in that category. Each dot signifies an individual gene identified as underexpressed or overexpressed, with their distribution across the categories visualized through violin plots. (B) RNA expression log₂ fold-change estimates of glutathione transferase genes annotated in the C. elegans genome across all mutants compared with their controls. (C) An acute time course of oxidative stress survival for large subunit RP mutants (first plot, rpl-5(0)/+ and rpl-33(0)/+) and small subunit RP mutants (second plot, rps-23(0)/+ and rps-10(0)/+), alongside wild-type control strains and daf-2(e13270) mutants serving as positive controls. All RP mutants showed significantly more resistance to acute oxidative stress (P < 0.001) compared with wild-type controls. rpl-5(0)/+; skn-1(zj15) double mutant animals were significantly less resistant to oxidative stress compared with rpl-5(0)/mutants (P = 0.016, third plot). Conversely, rpl-5(0)/+; daf-16(mu86) animals displayed similar responses to oxidative stress as rpl-5(0)/+ animals (P = 0.51, fourth plot). The “n=” on the graphs indicates the total number of animals analyzed. “n” indicates the total number of animals used in the study, and all experiments were performed using three biological replicates and all animals were grown at 16°C. rpl-33(0)/+³ in green, rpl-5(0)/+³ in orange, rps-10(0)/+¹ in blue, and rps-23(0)/+² in red. Balancer chromosomes are denoted as follows: +¹ = tmC20, +² = tmC5, +³ = mIn1. For statistical analysis of oxidative stress resistance, Log-rank analysis with Bonferroni correction was performed for multiple comparisons. (D) Log₂ fold-change estimates of SKN-1 targets in all RP mutants were plotted. SKN-1 targets were identified from differentially expressed genes upon the constitutive activation of SKN-1 (Nhan et al., 2019).