A systems level approach to understanding the role of protein-mRNA droplets in meiotic exit

The complex cell division process of meiosis ensures the formation of haploid gametes through two rounds of chromosome segregation after one round of DNA replication. How cells limit meiosis to two and only two divisions is poorly understood. In budding yeast, autophagy degrades the RNA-binding protein Rim4 in meiosis II (Wang et al. Dev. Cell 52 (2020)), which has been shown to form aggregated fibrils that bind various mRNAs to prevent their translation. Liquid-liquid phase separated condensates consisting of key molecules together with other proteins or RNA have been shown to be important in the proper execution of a variety of cellular regulatory processes in a spatially and temporally controlled manner through different mechanisms. Several of the mRNAs bound by Rim4 encode important regulators of meiosis II and meiotic exit. Indeed, with inhibition of autophagy, Rim4-mRNA droplets persist and cells fail to exit meiosis properly. To investigate the role of Rim4-mRNA droplets in the regulation of meiotic exit, we have constructed a parsimonious model of meiotic termination. Combined with experimental analysis, we describe the dynamics of key constituents governing irreversible exit demonstrating good agreement between the model and experiments. Notably, we show how disruption of droplet disintegration could result in exit failure and continued cell-cycle oscillations.