Distinct stages in stress granule assembly and disassembly

• Published in: eLife 2016-09, Vol.5
• Main Authors: Wheeler, Joshua R, Matheny, Tyler, Jain, Saumya, Abrisch, Robert, Parker, Roy
• Format: Article
• Language: English
• Subjects: Arsenites - pharmacology; Biochemistry; Cameras; Cell Biology; Cell Line, Tumor; Cell Survival - drug effects; Cycloheximide - pharmacology; Cytoplasmic Granules - drug effects; Cytoplasmic Granules - metabolism; Cytoplasmic Granules - ultrastructure; Digitonin - pharmacology; Experiments; Genetic aspects; Genetic translation; Glycols - pharmacology; Health aspects; HeLa Cells; Humans; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; liquid liquid phase separation; Membrane proteins; Microscopy; Neural circuitry; Peptide Chain Initiation, Translational - drug effects; phase transition; Proteins; Ribonucleic acid; Ribonucleoproteins - genetics; Ribonucleoproteins - metabolism; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-binding protein; RNP granule; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Sodium Compounds - pharmacology; Stress (Psychology); stress granule; Stress, Physiological; Time Factors; Translation initiation
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.18413

Stress granules are non-membrane bound RNA-protein (RNP) assemblies that form when translation initiation is limited and contain a biphasic structure with stable core structures surrounded by a less concentrated shell. The order of assembly and disassembly of these two structures remains unknown. Time course analysis of granule assembly suggests that core formation is an early event in granule assembly. Stress granule disassembly is also a stepwise process with shell dissipation followed by core clearance. Perturbations that alter liquid-liquid phase separations (LLPS) driven by intrinsically disordered protein regions (IDR) of RNA binding proteins in vitro have the opposite effect on stress granule assembly in vivo. Taken together, these observations argue that stress granules assemble through a multistep process initiated by stable assembly of untranslated mRNPs into core structures, which could provide sufficient high local concentrations to allow for a localized LLPS driven by IDRs on RNA binding proteins.