"On the Biosynthetic Mechanism Coupling Cell Growth to Division"

While cells of a given type span a large range of sizes, most proteins and mRNA are maintained at constant, size independent, concentrations. This raises the question of how cells can achieve size-dependent signals coordinating growth and division. Recently, we showed that budding yeast size control results from cell size-independent synthesis of the cell cycle inhibitor Whi5 and size-proportional synthesis of the cell cycle activator Cln3. Larger cells have a higher ratio of cell cycle activator to inhibitor, which triggers division. This raised two key questions: (1) To what extent do individual genes’ expression deviate from constant concentration? (2) What are the molecular mechanisms that determine whether gene expression depends on cell size? To address these questions, we examined the yeast GFP-fusion library. We identified approximately 200 proteins whose abundance does not scale with cell size. Many of these genes are involved in membrane transport and DNA-templated processes, which do not scale proportionally with cell size. A targeted analysis of WHI5 and histone genes suggest cells employ both transcriptional control and protein degradation for coordinating gene expression with size. Thus, our work demonstrates a functional role for differential size-dependency of protein synthesis and gives insights into the underlying molecular mechanisms. We also discuss how these principles can be applied to understanding how growth and division are coupled in mammalian cells.