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Datasets and analysis code for "Context-dependent RAC–NAC cooperation in yeast" (Janik et al)

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This item contains the datasets and R scripts underlying the analyses and figures presented in this study.The ribosome-associated complex (RAC) and nascent polypeptide-associated complex (NAC) are conserved cotranslational chaperone systems, but how they functionally interact remains poorly defined. Using a panel of Saccharomyces cerevisiae strains containing all pairwise combinations of yeast, human, or deleted RAC and NAC, we examined proliferative growth, chronological lifespan, unfolded protein response (UPR) induction, and protein aggregation. Under normal conditions and mild heat stress, colony growth was governed by a strong RAC × NAC interaction: yeast RAC and yeast NAC acted synergistically to produce the largest colonies, while NAC was detrimental without functional RAC. ER stress reorganized this relationship; RAC source no longer predicted growth alone, and the yeast RAC–yeast NAC pairing, optimal under normal conditions, became antagonistic and produced the smallest colonies. Chronological lifespan revealed a contrasting pattern: yeast RAC was consistently associated with reduced survival, while yeast NAC was generally protective, producing a growth–longevity trade-off in which the combination that maximized proliferation was among the least favorable for survival. Unlike growth, where ER stress reversed the RAC×NAC interaction's sign, the interaction governing lifespan remained sub-additive under both normal growth and ER stress. Mechanistically, yeast RAC attenuated tunicamycin-induced Kar2 expression and reduced protein aggregation, while NAC had no significant effect on either measure. Together, these findings indicate that RAC and NAC function as an integrated cotranslational proteostasis network in which the native yeast combination promotes rapid proliferation but becomes maladaptive during ER stress and is linked to reduced lifespan, revealing a context-dependent trade-off between growth and longevity.

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