title: Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae.
abstract: Stress granules and P-bodies are conserved assemblies of nontranslating mRNAs in eukaryotic cells that can be related to RNA-protein aggregates found in some neurodegenerative diseases. Herein, we examine how the Hsp70/Hsp40 protein chaperones affected the assembly and disassembly of stress granules and P-bodies in yeast. We observed that Hsp70 and the Ydj1 and Sis1 Hsp40 proteins accumulated in stress granules and defects in these proteins led to decreases in the disassembly and/or clearance of stress granules. We observed that individual Hsp40 proteins have different effects on stress granules with defects in Ydj1 leading to accumulation of stress granules in the vacuole and limited recovery of translation following stress, which suggests that Ydj1 promotes disassembly of stress granules to promote translation. In contrast, defects in Sis1 did not affect recovery of translation, accumulated cytoplasmic stress granules, and showed reductions in the targeting of stress granules to the vacuole. This demonstrates a new principle whereby alternative disassembly machineries lead to different fates of components within stress granules, thereby providing additional avenues for regulation of their assembly, composition, and function. Moreover, a role for Hsp70 and Hsp40 proteins in stress granule disassembly couples the assembly of these stress responsive structures to the proteostatic state of the cell.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80303, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Walters
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80303, USA Howard Hughes Medical Institute, Boulder, Colorado 80303, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Muhlrad
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80303, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80303, USA Howard Hughes Medical Institute, Boulder, Colorado 80303, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Parker
mesh_terms: D001343:Autophagy; D003594:Cytoplasmic Granules / Q000502:physiology*; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D014617:Vacuoles / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C070320:SIS1 protein, S cerevisiae; C090869:SSA3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070319:YDJ1 protein, S cerevisiae
keywords: Hsp70; Sis1; Ydj1; stress granules