Coupling of protein synthesis with cell division

About This Grant

Cell growth and division are tightly linked processes, and protein synthesis plays a central role in regulating both. This research aims to uncover how cells coordinate protein synthesis with cell division. It exploits the experimental advantages of budding yeast to tackle this problem. Project 1 will answer how nutrients adjust the synthesis of Cak1. This enzyme phosphorylates and activates Cdk, the master regulator of cell division. The proposed experiments will define the translational control of CAK1 as a function of nutrient status. They will provide a mechanism that ties Cdk activation and cell division to growth conditions. Project 2 focuses on the translational control of CLN3. This mRNA encodes a G1 cyclin that turns Cdk on, committing cells to divide. Preliminary evidence points to a heightened ribosomal association of CLN3 early in the cell cycle. The proposed experiments will measure CLN3 mRNA localization and translation at the single-cell level. They will also identify RNA-binding proteins that interact with CLN3 using proximity labeling. Project 3 will elucidate the translational control of ADE17 in the cell cycle. Ade17 is a crucial enzyme of one-carbon metabolism and purine biosynthesis. Changes in Ade17 levels affect the size of cells and their commitment to divide. The proposed experiments will answer how translational control of ADE17 mRNA is linked to the purine flux needed for cell cycle progression. This project will provide significant insights into how protein synthesis and metabolic cues converge on the machinery for cell division. The results will have broad implications for controlling cell proliferation.