Phosphorylation of the RNA-binding protein Zfs1 modulates sexual differentiation in fission yeast

Sexual differentiation in the fission yeast Schizosaccharomyces pombe promotes cell cycle arrest and extensive changes in gene expression, resulting in cell-to-cell fusion, the exchange of hereditary material and specialized cell division. These events are detrimental to the cell if they are triggered in inappropriate conditions, and therefore the decision to differentiate must be precisely controlled. Here, we investigated the role of the RNA-binding protein Zfs1 in this process by identifying its targets and characterizing novel post-translational regulatory mechanisms. We found that Zfs1 negatively regulates the G1 cyclin Puc1, and deregulated Puc1 levels inhibit differentiation in the zfs1Δ mutant. We also found that Zfs1 undergoes phosphorylation, which is stimulated upon nitrogen depletion or inhibition of the TOR pathway. Phosphorylation of Zfs1 modulates accumulation of Puc1 and plays an important role in the response of the cell to sexual differentiation signals. We propose that Zfs1 functions as an integrator of nutrient information to modulate sexual differentiation, contributing to the establishment of the differentiation-activating threshold.