Coupling of Protein Synthesis with Cell Division
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abstract
Protein synthesis governs if, how fast, and how many times cells divide. Yet how protein synthesis islinked molecularly with cell division is unknown. We use budding yeast as a model system to answer thisproblem. Because yeast has unique properties, suited for genetic and biochemical experiments. Newmethodologies can identify transcripts that engage with the protein synthesis machinery, the ribosomes,in the process of translation. For the first time in the field, we applied this ribosome profiling methodologyin synchronously dividing cells that maintained the physiological coupling of protein synthesis with theirdivision. In this collaborative proposal, we will leverage these findings to tackle the long-standing problemof protein synthesis requirements for cell divisions. In Aim 1, we will determine how translational controlof lipogenic enzymes regulates the remodeling of cellular membranes during cell division. Furthermore,we will determine how protein synthesis adjusts the production of proteins that trigger duplication of thespindle pole body, an essential part of the machinery of chromosome segregation. We will also identifytranslationally regulated mRNAs under dietary restriction, which changes the size of cells and increasesthe number of times cells divide before they die. In Aim 2, we will extend ribosome profiling to settings ofspecific ribosomal protein mutants that delay cell division and increase lifespan. These geneticinterventions will enable us to identify mRNA targets of translational control that underpin cell divisionand replicative longevity when protein synthesis is limited. Knowing how translational control affects thetiming and number of cell divisions will reveal fundamental links between cell growth, protein synthesis,cell division and aging, enabling novel therapeutic interventions in proliferative diseases.
