The UPR drives gametogenesis via an unexpected response, coordinating translation and ER structure

Stress responses, including the unfolded protein response (UPR), are commonly studied via induction with harsh exogenous stressors, leaving endogenous functions of these pathways less well understood. We found that the endogenous UPR that precedes meiosis in budding yeast is required for gamete production but diverges dramatically from previously defined UPR outputs, with only a few characterized UPR targets induced, and mildly. The role of this UPR can be replaced by increasing ER chaperones, reducing bulk translation, or impairing the machinery for protein translocation into the ER. ER integrity appears compromised in premeiotic cells lacking the UPR, as foci of reticulon proteins are seen and correlate strongly with an inability of cells to enter meiosis. These findings indicate that physiological UPR activation supports proteostasis and normal ER structure, preparing cells for meiotic entry by reducing the load of proteins that enter the ER. Overall, our study reveals surprising features of a physiological UPR induction that enables a cell-fate decision.