ABSTRACT
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: X.X., S.M., A.E., T.F., M.K.; Methodology: X.X., S.M., A.E., T.F., M.K.; Validation: X.X., S.M., A.E., T.F., M.K.; Investigation: X.X., S.M., A.E., M.K.; Resources: H.K.; Writing - original draft: X.X., M.K.; Writing - review & editing: A.E., T.F., Y.S., M.K.; Visualization: X.X., M.K.; Supervision: T.F., M.K.; Funding acquisition: M.K.
Funding
This work was supported by the Japan Society for the Promotion of Science [KAKENHI JP24112003 to M.K.].
Supplementary information
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.210856.supplemental
- Received September 13, 2017.
- Accepted March 16, 2018.
- © 2018. Published by The Company of Biologists Ltd
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