TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle

Recent studies have revealed that the growth rate of budding yeast and mammalian cells varies during the cell cycle. By linking a multitude of signals to cell growth, the highly conserved Target of Rapamycin Complex 1 (TORC1) and Protein Kinase A (PKA) pathways are prime candidates for mediating the dynamic coupling between growth and division. However, measurements of TORC1 and PKA activity during the cell cycle are still lacking. Following the localization dynamics of two TORC1 and PKA targets via time-lapse microscopy in hundreds of yeast cells, we found that the activity of these pathways towards ribosome biogenesis fluctuates in synchrony with the cell cycle even under constant external conditions. Mutations of upstream TORC1 and PKA regulators suggested that internal metabolic signals partially mediate these activity changes. Our study reveals a new aspect of TORC1 and PKA signaling, which will be important for understanding growth regulation during the cell cycle.

Size-independent mRNA synthesis and chromatin-based partitioning mechanisms generate and maintain constant amounts of protein per cell

SummaryCell size and biosynthesis are inextricably linked. As cells grow, total protein synthesis increases in proportion to cell size so that protein concentrations remain constant. As an exception, the budding yeast cell-cycle inhibitor Whi5 is synthesized in a constant amount per cell cycle, so that it is diluted in large cells to trigger division. Here, we show that this size-independent expression of Whi5 results from size-independent transcription. A screen for similar genes identified histones as the major class of size-independent transcripts during the cell cycle, consistent with histone synthesis being coupled to genome content rather than cell size. However, during asymmetric division size-independent transcription is insufficient for size-independent protein expression and chromatin-binding ensures equal amounts of protein are partitioned to unequally sized cells to maintain size-independent protein amounts. Thus, specific transcriptional and partitioning mechanisms determine size-independent protein expression to control cell size.

Abundances of transcripts, proteins, and metabolites in the cell cycle of budding yeast reveal coordinate control of lipid metabolism

In several systems, including budding yeast, cell cycle-dependent changes in the transcriptome are well studied. In contrast, few studies queried the proteome during cell division. There is also little information about dynamic changes in metabolites and lipids in the cell cycle. Here, the authors present such information for dividing yeast cells.

A Hybrid Stochastic Model of the Budding Yeast Cell Cycle

The growth and division of eukaryotic cells are regulated by complex, multi-scale networks. In this process, the mechanism controlling cell cycle progression has to be robust against inherent noise in the system. In this paper, a hybrid stochastic model is developed to study the effects of noise on the control mechanism of the budding yeast cell cycle. The modeling approach leverages, in a single multi-scale model, the advantages of two regimes: 1) the computational efficiency of a deterministic approach, and 2) the accuracy of stochastic simulations. Our results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements.