Comparative analysis of genetic regulation in dormant cells of fission yeast, turquoise killifish and human cancer

Dormancy is a conserved survival strategy observed across a wide range of organisms, from unicellular microbes to vertebrates, characterized by reversible cell-cycle arrest and reduced metabolic activity. In this study, we conducted a comparative analysis of genetic regulation in dormant cells using three model systems: fission yeast spores (Schizosaccharomyces pombe), diapause embryos of the turquoise killifish (Nothobranchius furzeri), and dormant human cancer cells. By integrating transcriptomic, proteomic, and large-scale functional data from a barcoded mutant screen, we identified conserved regulatory mechanisms that govern dormancy, focusing on ribosomal proteins and autophagy-related processes. Our findings reveal that, despite the distinct physiological and developmental contexts, these dormant states share a core regulatory signature. Ribosomal protein mRNAs are consistently upregulated during dormancy across species, even as protein levels remain suppressed, suggesting a conserved mechanism of post-transcriptional regulation. Functional analysis using a bar-seq screen in yeast spores confirmed that ribosomal protein mutants exhibit reduced spore longevity but increased heat-shock resistance, highlighting a critical role for ribosomal proteins in maintaining dormancy viability. Similarly, autophagy-related genes are upregulated across all dormant stages and are essential for resilience against stress conditions. However, their deletion intriguingly extended spore lifespan, indicating autophagy's complex and context-dependent role in dormancy regulation. These results provide insights into shared molecular pathways that enable dormancy across diverse biological systems and offer a framework for understanding dormancy.