Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities

J Cell Sci. 2018 Apr 12;131(8):jcs210856. doi: 10.1242/jcs.210856.


Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains.This article has an associated First Person interview with the first author of the paper.

Keywords: Deubiquitylase; Stress granule; USP13; USP5; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endopeptidases / metabolism*
  • Humans
  • Hydrolysis
  • Protein Binding
  • Ubiquitin-Specific Proteases
  • Ubiquitination


  • Endopeptidases
  • USP13 protein, human
  • Ubiquitin-Specific Proteases
  • ubiquitin isopeptidase