Assembly and function of the amyloid-like translational repressor Rim4 is coupled with nutrient conditions

Amyloid-like protein assemblies have been associated with toxic phenotypes because of their repetitive and stable structure. However, evidence that cells exploit these structures to control function and activity of some proteins in response to stimuli has questioned this paradigm. How amyloid-like assembly can confer emergent functions and how cells couple assembly with environmental conditions remains unclear. Here, we study Rim4, an RNA-binding protein that forms translation-repressing assemblies during yeast meiosis. We demonstrate that in its assembled and repressive state, Rim4 binds RNA more efficiently than in its monomeric and idle state, revealing a causal connection between assembly and function. The Rim4-binding site location within the transcript dictates whether the assemblies can repress translation, underscoring the importance of the architecture of this RNA-protein structure for function. Rim4 assembly depends exclusively on its intrinsically disordered region and is prevented by the Ras/protein kinase A signaling pathway, which promotes growth and suppresses meiotic entry in yeast. Our results suggest a mechanism whereby cells couple a functional protein assembly with a stimulus to enforce a cell fate decision. imageThe RNA-binding protein Rim4, required for meiosis in yeast, forms amyloid-like assemblies that repress translation of select messenger RNAs. Here, it is shown that PKA inactivation triggers the formation of Rim4 assemblies and that these structures repress translation by promoting efficient RNA binding and by preventing start codon access by ribosomes.Rim4 forms SDS-resistant assemblies that repress translation of select messenger RNAs during meiosis.Rim4 assembly is necessary for function as it promotes efficient binding to target mRNAs.The architecture of the RNA-Rim4 assembly structure dictates productive translational regulation.Active PKA prevents Rim4 amyloid-like assembly. Amyloid-like assembly of the yeast RNA-binding protein Rim4, which is triggered by PKA inactivation, stimulates Rim4 target binding and translational repression.image