Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis.
Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis.
复制标题
DOI：
10.1016/j.cell.2015.08.060
复制
发表时间：
2015-10-08
期刊：
影响因子：
64.5
通讯作者：
Amon A
中科院分区：
文献类型：
--
作者：
Berchowitz LE;Kabachinski G;Walker MR;Carlile TM;Gilbert WV;Schwartz TU;Amon A
配子发生需要消息特定的翻译控制。在酵母中，RNA 结合蛋白 Rim4 介导许多 mRNA 的翻译抑制，包括 B 型细胞周期蛋白 CLB3，这对于建立减数分裂染色体分离模式至关重要。在这里，我们证明 Rim4 形成淀粉样蛋白样聚集体，并且 Rim4 的淀粉样蛋白样形式是该蛋白质的活性翻译抑制形式。我们的数据进一步表明 Rim4 聚合是一个发育调控过程。饥饿会诱导单体 Rim4 转化为淀粉样蛋白样聚集体，从而激活该蛋白质以抑制翻译。在减数分裂 II 开始时，Rim4 聚集体突然降解，从而开始翻译。尽管淀粉样蛋白因其在阿尔茨海默病、帕金森病和糖尿病等疾病的病因学中通过形成有毒蛋白质聚集体而闻名，但我们的研究结果表明，细胞可以利用淀粉样蛋白聚集体作为配子发生的中央调节剂。
Message specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here we show that Rim4 forms amyloid-like aggregates and that it is the amyloid-like form of Rim4 that is the active, translationally repressive form of the protein. Our data further show that Rim4 aggregation is a developmentally regulated process. Starvation induces the conversion of monomeric Rim4 into amyloid-like aggregates thereby activating the protein to bring about repression of translation. At the onset of meiosis II, Rim4 aggregates are abruptly degraded allowing translation to commence. Although amyloids are best known for their role in the etiology of diseases such as Alzheimer’s, Parkinson’s, and diabetes by forming toxic protein aggregates, our findings show that cells can utilize amyloid-like protein aggregates to function as central regulators of gametogenesis.