Differential Scaling of Gene Expression with Cell Size May Explain Size Control in Budding Yeast

Yeast cells must grow to a critical size before committing to division. It is unknown how size is measured. We find that as cells grow, mRNAs for some cell-cycle activators scale faster than size, increasing in concentration, while mRNAs for some inhibitors scale slower than size, decreasing in concentration. Size-scaled gene expression could cause an increasing ratio of activators to inhibitors with size, triggering cell-cycle entry. Consistent with this, expression of the CLN2 activator from the promoter of the WHI5 inhibitor, or vice versa, interfered with cell size homeostasis, yielding a broader distribution of cell sizes. We suggest that size homeostasis comes from differential scaling of gene expression with size. Differential regulation of gene expression as a function of cell size could affect many cellular processes.