Cell Cycle Laboratory, The Francis Crick Institute, London NW1 1AT, UK
Bioinformatics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
J Cell Sci. 2017 Dec 15;130(24):4144-4154. doi: 10.1242/jcs.208066. Epub 2017 Oct 30.
Sexual differentiation in the fission yeast 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 Δ 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.
裂殖酵母中的性别分化促进细胞周期停滞和基因表达的广泛改变，导致细胞融合、遗传物质的交换和特化的细胞分裂。如果这些事件在不合适的条件下被触发，对细胞是有害的，因此分化的决定必须被精确控制。在这里，我们通过鉴定其靶标和描述新的翻译后调控机制来研究 RNA 结合蛋白 Zfs1 在这个过程中的作用。我们发现 Zfs1 负调控 G1 周期蛋白 Puc1，并且 Puc1 水平的失调抑制 Δ 突变体中的分化。我们还发现 Zfs1 经历磷酸化，这是在氮源耗尽或 TOR 途径抑制时被刺激的。Zfs1 的磷酸化调节 Puc1 的积累，并在细胞对性分化信号的反应中起重要作用。我们提出 Zfs1 作为营养信息的整合因子来调节性别分化，有助于建立分化激活阈值。
