A minimal model for the role of Rim4 in regulating meiotic exit in budding yeast

Meiosis ensures formation of haploid gametes through two rounds of chromosome segregation after one round of DNA replication. How this complex cell cycle process is restricted to two and only two divisions is poorly understood. In budding yeast, RNA-binding protein Rim4 binds various mRNAs to prevent their translation. At the onset of meiosis II, phosphorylation and degradation of Rim4, along with the concomitant release of sequestered mRNA, has an important role in ensuring meiotic exit. Building on previous work, we developed a parsimonious mathematical model of meiotic termination that elucidates the role of Rim4-mRNA release and translation of AMA1 mRNA in the fidelity of meiotic exit. Central to our model is the accumulation of Ama1 protein, a meiosis-specific activator of APC/C. Our mathematical model predicted further outcomes, which we tested experimentally. We found that either slowing Rim4 degradation or disrupting APC/C^Ama1 activity delayed meiosis II. In some cells, this disruption prevented meiotic exit entirely, leading them to re-enter cell cycle oscillations after meiosis II. These findings demonstrate that the timely activation of this regulatory network is crucial for ensuring irreversible meiotic exit.