The feedback of ribosome biogenesis on TORC1 activity in Saccharomyces cerevisiae

Target of rapamycin (TOR) protein kinases belong to the family of phosphatidylinositol kinase-related kinases. They are structurally and functionally conserved in all eukaryotes. Their dysregulation in mammalian cells is thought to contribute to many forms of cancer. Tor kinases function in two different multiprotein complexes that play central roles in the cell physiology, such as response to nutrients, stress, intracellular energy state, the regulation of ribosome biogenesis, growth control, etc.

Ribosome biogenesis is the most energy-consuming anabolic process in the cell, which needs to be well controlled especially in response to stress conditions when energy should be saved. It is known that TORC1 regulates the activity of all three RNA polymerases in the cell largely through Sch9 (a Ser/Thr protein kinase of the AGC family) and through Sfp1 (a Zinc-finger transcription factor). Interestingly, it was shown that Sfp1 and Sch9 reciprocally regulate TORC1 activity, presumably via ribosome biogenesis. The aim of my project is to better characterize the nature of this feedback. I plan to disrupt various nodes of ribosome biogenesis to reveal the most important step for the feedback. For this we chose essential and conserved genes functioning at various stages of ribosome biogenesis. To inhibit expression of these genes and to degrade already present proteins I will use auxin-degron systems. As a readout of TORC1 activity we will check the phosphorylation changes of Sch9 and Sfp1 upon disruption of ribosome biogenesis stages. The ultimate goal is to understand how TORC1 is regulated in response to intracellular metabolic cues.