RNA-Seq profiling of S. Cerevisiae WT BY4741 cells and MOH1-knockout mutants of BY4741 cells (moh1?) after growth on YPD-Agar for 40 hours
The Yippee-like (YPEL) proteins are a conserved eukaryotic gene family implicated in proliferation, senescence, and stress adaptation. In humans, five paralogs (YPEL1–YPEL5) are widely expressed and encode proteins with high sequence similarity, but the molecular basis of their functions remains poorly defined. Functional redundancy among YPEL paralogs complicates the clarification of their individual roles. The budding yeast Saccharomyces cerevisiae has a single ortholog, MOH1, which is involved in survival and stress responses and can be functionally complemented by human YPELs. However, the cellular function of MOH1 has yet to be elucidated. Here, we investigated the function of MOH1 in S. cerevisiae. Deletion of MOH1 (moh1?) conferred sensitivity to sodium azide and sulfuric acid but increased resistance to hydrogen peroxide and acetic acid. Moh1 protein levels decreased upon hydrogen peroxide treatment and increased following sulfuric acid exposure, indicating stress-dependent regulation. Light and scanning electron microscopy analyses revealed that moh1? cells are constitutively rounder, tend to form clumps, and exhibit rough surface features, signifying altered cellular architecture. RNA profiling and FTIR spectroscopy revealed transcriptional reprogramming and metabolic remodeling in moh1? cells, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Intracellular ROS assays revealed that resistance to hydrogen peroxide results from reduced cellular uptake caused by altered membrane permeability, rather than from differences in mitochondrial ROS generation. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, influencing membrane permeability and conferring selective stress resistance in S. cerevisiae.
The Yippee-like (YPEL) proteins are a conserved eukaryotic gene family implicated in proliferation, senescence, and stress adaptation. In humans, five paralogs (YPEL1–YPEL5) are widely expressed and encode proteins with high sequence similarity, but the molecular basis of their functions remains poorly defined. Functional redundancy among YPEL paralogs complicates the clarification of their individual roles. The budding yeast Saccharomyces cerevisiae has a single ortholog, MOH1, which is involved in survival and stress responses and can be functionally complemented by human YPELs. However, the cellular function of MOH1 has yet to be elucidated. Here, we investigated the function of MOH1 in S. cerevisiae. Deletion of MOH1 (moh1?) conferred sensitivity to sodium azide and sulfuric acid but increased resistance to hydrogen peroxide and acetic acid. Moh1 protein levels decreased upon hydrogen peroxide treatment and increased following sulfuric acid exposure, indicating stress-dependent regulation. Light and scanning electron microscopy analyses revealed that moh1? cells are constitutively rounder, tend to form clumps, and exhibit rough surface features, signifying altered cellular architecture. RNA profiling and FTIR spectroscopy revealed transcriptional reprogramming and metabolic remodeling in moh1? cells, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Intracellular ROS assays revealed that resistance to hydrogen peroxide results from reduced cellular uptake caused by altered membrane permeability, rather than from differences in mitochondrial ROS generation. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, influencing membrane permeability and conferring selective stress resistance in S. cerevisiae.
European Bioinformatics Institute