Distinct stages in stress granule assembly and disassembly.
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.
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States.
Joshua R
0000-0002-7315-8269
JR
Wheeler
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States.
Tyler
T
Matheny
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States.
Saumya
S
Jain
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States.
Robert
R
Abrisch
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States.|Howard Hughes Medical Institute, University of Colorado, Boulder, United States.
Roy
0000-0002-8412-4152
R
Parker
D018053:Arsenites / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004072:Digitonin / Q000494:pharmacology; D006018:Glycols / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000235:genetics* / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D017670:Sodium Compounds / Q000494:pharmacology; D013312:Stress, Physiological; D013997:Time Factors
D018053:Arsenites; D006018:Glycols; D064267:Intrinsically Disordered Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D017670:Sodium Compounds; C026452:messenger ribonucleoprotein; C017947:sodium arsenite; D003513:Cycloheximide; D004072:Digitonin; C027765:hexamethylene glycol
RNP granule; S. cerevisiae; biochemistry; cell biology; human; liquid liquid phase separation; phase transition; stress granule