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

EMBO J. 2023 Dec 1;42(23):e113332. doi: 10.15252/embj.2022113332. Epub 2023 Nov 3.

Abstract

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.

Keywords: RNA-binding proteins; amyloid-like assemblies; meiosis; nutrient signaling; protein translation.

MeSH terms

  • Amyloidogenic Proteins / metabolism
  • Meiosis
  • Nutrients
  • RNA / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Amyloidogenic Proteins
  • RNA
  • Rim4 protein, S cerevisiae
  • RNA-Binding Proteins