Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis

• Published in: Cell Vol. 163; no. 2; pp. 406 - 418
• Main Authors: Berchowitz, Luke E., Kabachinski, Greg, Walker, Margaret R., Carlile, Thomas M., Gilbert, Wendy V., Schwartz, Thomas U., Amon, Angelika
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.10.2015
• Subjects: Amyloidogenic Proteins - chemistry; Amyloidogenic Proteins - metabolism; Animals; Cyclin B - genetics; Gametogenesis; Gene Expression Regulation; Male; Meiosis; Mice; Mice, Inbred C57BL; Protein Aggregates - drug effects; Protein Biosynthesis; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sodium Dodecyl Sulfate - pharmacology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2015.08.060

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. [Display omitted] •Amyloid-like aggregation of the RNA-binding protein Rim4 controls gametogenesis•The amyloid-like form of Rim4 is active and represses translation•Aggregation and clearance of Rim4 are developmentally regulated•Amyloid-like aggregation of RNA-binding proteins during gametogenesis is conserved Amyloid-like aggregation of the RNA-binding protein Rim4 controls gametogenesis by repressing message-specific translation.