Rates of global cellular translation and transcription during cell growth and the cell cycle in fission yeast

Abstract

Proliferating eukaryotic cells grow and undergo cycles of cell division. Growth is continuous whilst the cell cycle consists of discrete events. How the production of biomass is controlled as cells increase in size and proceed through the cell cycle is important for understanding the regulation of global cellular growth. This has been studied for decades but has not yielded consistent results. Previous studies investigating how cell size, the amount of DNA, and cell cycle events affect the global cellular production of proteins and RNA molecules have led to highly conflicting results, probably due to perturbations induced by the synchronisation methods used. To avoid these perturbations, we have developed a system to assay unperturbed exponentially growing populations of fission yeast cells. We generated thousands of single-cell measurements of cell size, of cell cycle stage, and of the levels of global cellular translation and transcription. This has allowed us to determine how cellular changes arising from progression through the cell cycle and cells growing in size affect global cellular translation and transcription. We show that translation scales with size, and additionally increases at late S-phase/early G2, then increases early in mitosis and decreases later in mitosis, suggesting that cell cycle controls are 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.