A Super-Assembly of Whi3 Encodes Memory of Deceptive Encounters by Single Cells during Yeast Courtship

•Yeast cells unproductively exposed to pheromone enter a pheromone refractory state•The refractory state is memorized by mother cells, not inherited by daughter cells•Memory is encoded by super-assembly and inactivation of the mRNA-binding protein Whi3•Whi3 is a mnemon, i.e., protein-establishing memory through its super-assembly

SummaryCellular behavior is frequently influenced by the cell’s history, indicating that single cells may memorize past events. We report that budding yeast permanently escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating attempt, i.e., not reaching their putative partner within reasonable time. This acquired behavior depends on super-assembly and inactivation of the G1/S inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition. Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN domains, counteracted by Hsp70, and stable over generations. Unlike prion aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to the mother cell. We propose that such polyQ- and polyN-based elements, termed here mnemons, act as cellular memory devices to encode previous environmental conditions.

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