Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis

被引:125
作者
Berchowitz, Luke E. [1 ,2 ]
Kabachinski, Greg [3 ]
Walker, Margaret R. [1 ,2 ]
Carlile, Thomas M. [3 ]
Gilbert, Wendy V. [3 ]
Schwartz, Thomas U. [3 ]
Amon, Angelika [1 ,2 ,3 ]
机构
[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[2] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[3] MIT, Dept Biol, Cambridge, MA 02139 USA
关键词
RNA-BINDING PROTEINS; AGGREGATES IN-VITRO; SACCHAROMYCES-CEREVISIAE; PRION; GENE; GRANULES; MEIOSIS; OLIGOMERS; DOMAINS; DISEASE;
D O I
10.1016/j.cell.2015.08.060
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:406 / 418
页数:13
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