The cell cycle and cell size influence the rates of global cellular translation and transcription in fission yeast

Abstract

How the production of biomass is controlled as cells increase in size and proceed through the cell cycle events is important for understanding the regulation of global cellular growth. This has been studied for decades but has not yielded consistent results, probably due to perturbations induced by the synchronisation methods used in most previous studies. To avoid this problem, we have developed a system to analyse unperturbed exponentially growing populations of fission yeast cells. We generated thousands of fixed single‐cell measurements of cell size, cell cycle stage and the levels of global cellular translation and transcription. We show that translation scales with size, and additionally, increases at late S‐phase/early G2 and early in mitosis and decreases later in mitosis, suggesting that cell cycle controls are also operative over global cellular translation. Transcription increases with both size and the amount of DNA, suggesting that the level of transcription of a cell may be the result of a dynamic equilibrium between the number of RNA polymerases associating and disassociating from DNA. image Perturbations induced by synchronization procedures have hampered the study of how biomass production is linked to the cell cycle and cell growth. Here, an assay using exponentially growing populations of fission yeast is developed to understand the influences of the cell cycle and cell size on the global rates of production of proteins and RNA in unperturbed cells. Both global transcription and translation increase with cell size. In large cells, global translation becomes limited by cell size earlier than transcription does. Global translation is regulated by cell cycle events, increasing at the S/G2 transition and early in mitosis, and deceasing later in mitosis. Global transcription appears to increase through S phase.