Clearance of an amyloid-like translational repressor is governed by 14-3-3 proteins

• Published in: Cell reports (Cambridge) Vol. 39; no. 5; p. 110753
• Main Authors: Herod, S. Grace, Dyatel, Annie, Hodapp, Stefanie, Jovanovic, Marko, Berchowitz, Luke E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.05.2022; Elsevier
• Subjects: 14-3-3 proteins; 14-3-3 Proteins - metabolism; amyloid; Amyloid - metabolism; Amyloidogenic Proteins - metabolism; chaperones; CP: cell biology; CP: molecular biology; gametogenesis; meiosis; Protein Aggregates; protein homeostasis; RNA-binding proteins; RNA-Binding Proteins - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; 14-3-3 proteins; amyloid; meiosis; CP: molecular biology; gametogenesis; protein homeostasis; CP: cell biology; RNA-binding proteins; protein aggregates; chaperones
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110753

Amyloids are fibrous protein aggregates associated with age-related diseases. While these aggregates are typically described as irreversible and pathogenic, some cells use reversible amyloid-like structures that serve important functions. The RNA-binding protein Rim4 forms amyloid-like assemblies that are essential for translational control during Saccharomyces cerevisiae meiosis. Rim4 amyloid-like assemblies are disassembled in a phosphorylation-dependent manner at meiosis II onset. By investigating Rim4 clearance, we elucidate co-factors that mediate clearance of amyloid-like assemblies in a physiological setting. We demonstrate that yeast 14-3-3 proteins bind to Rim4 assemblies and facilitate their subsequent phosphorylation and timely clearance. Furthermore, distinct 14-3-3 proteins play non-redundant roles in facilitating phosphorylation and clearance of amyloid-like Rim4. Additionally, we find that 14-3-3 proteins contribute to global protein aggregate homeostasis. Based on the role of 14-3-3 proteins in aggregate homeostasis and their interactions with disease-associated assemblies, we propose that these proteins may protect against pathological protein aggregates. [Display omitted] •Yeast 14-3-3 proteins Bmh1 and Bmh2 bind to Rim4 amyloid-like assemblies in meiosis•Bmh1 and Bmh2 act non-redundantly in phosphorylation-mediated clearance of Rim4•14-3-3 proteins facilitate Rim4 phosphorylation by Ime2•14-3-3 proteins contribute to global protein aggregate homeostasis Amyloids are protein aggregates associated with age-related diseases. Herod et al. demonstrate that yeast 14-3-3 proteins play critical roles in the clearance of functional amyloid-like assemblies. Additionally, 14-3-3 proteins contribute to global protein aggregate homeostasis. Based on these findings, they propose that 14-3-3 proteins may protect against pathological protein aggregates.