Molecular Biology Institute of Barcelona, Spanish National Research Council, Catalonia, Spain.
Department of Microbiology and Immunology, Zagazig University, Zagazig, Egypt.
J Cell Biol. 2021 Mar 1;220(3). doi: 10.1083/jcb.202005102.
Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk's subjugate SG dynamics to a conserved hysteretic switch.
应激颗粒（SGs）是保守的生物分子凝聚物，起源于多种应激条件。这些无膜细胞器包含非翻译的 mRNA 和多样化的亚蛋白组，但我们对其调节和功能相关性的了解仍处于起步阶段。在这里，我们描述了 SGs 和芽殖酵母 Cdk 的 Cdc28 之间的相互抑制相互作用。在作为 Start 的负调节剂发挥作用的 Cdc28 相互作用子中，我们已经鉴定出 Whi8，一种 RNA 结合蛋白，它定位于 SGs 并募集最上游 G1 细胞周期蛋白 CLN3 的 mRNA，以在应激下有效抑制翻译和 Cdk 失活。然而，Whi8 也有助于将 Cdc28 招募到 SGs 中，在那里它可以促进它们的溶解。正如相互抑制框架所预测的那样，SG 构成了一个双稳态系统，由 Cdk 调节。由于哺乳动物细胞显示出同源机制，我们提出特定的 mRNA 结合蛋白的相反功能和 Cdk 的从属作用使 SG 动力学受到保守的滞后开关的调节。
