The Interplay Between Disordered Regions in RNAs and Proteins Modulates Interactions Within Stress Granules and Processing Bodies

J Mol Biol. 2022 Jan 15;434(1):167159. doi: 10.1016/j.jmb.2021.167159. Epub 2021 Jul 16.

Abstract

Condensation, or liquid-like phase separation, is a phenomenon indispensable for the spatiotemporal regulation of molecules within the cell. Recent studies indicate that the composition and molecular organization of phase-separated organelles such as Stress Granules (SGs) and Processing Bodies (PBs) are highly variable and dynamic. A dense contact network involving both RNAs and proteins controls the formation of SGs and PBs and an intricate molecular architecture, at present poorly understood, guarantees that these assemblies sense and adapt to different stresses and environmental changes. Here, we investigated the physico-chemical properties of SGs and PBs components and studied the architecture of their interaction networks. We found that proteins and RNAs establishing the largest amount of contacts in SGs and PBs have distinct properties and intrinsic disorder is enriched in all protein-RNA, protein-protein and RNA-RNA interaction networks. The increase of disorder in proteins is accompanied by an enrichment in single-stranded regions of RNA binding partners. Our results suggest that SGs and PBs quickly assemble and disassemble through dynamic contacts modulated by unfolded domains of their components.

Keywords: RNA and proteins; fuzzy interactions; interaction networks; liquid-liquid phase separation; structural disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Processing Bodies / genetics*
  • Processing Bodies / metabolism
  • RNA / chemistry*
  • RNA / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Stress Granules / genetics*
  • Stress Granules / metabolism

Substances

  • RNA-Binding Proteins
  • RNA