Clearance of an Amyloid-Like Translational Repressor is Governed by 14-3-3 Proteins

Abstract

Amyloids are fibrous protein aggregates associated with age-related diseases. While these aggregates are typically described as irreversible and pathogenic, some cells utilize reversible amyloid-like structures that serve important functions. The RNA-binding protein Rim4 forms amyloid-like assemblies that are essential for translational control during S. cerevisiae meiosis. Rim4 amyloid-like assemblies are disassembled in a phosphorylation-dependent manner. By investigating Rim4 clearance, we elucidate how phosphorylation contributes to reversal and clearance of amyloid-like assemblies in a physiological setting. We demonstrate that yeast 14-3-3 proteins link Rim4 to its kinase, thus facilitating phosphorylation and timely clearance of Rim4 assemblies. 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.