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
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
Call for papers – Reconstituting cell biology
Deadline for submissions: 1 May 2018
We are now accepting submissions for our upcoming special issue on ‘Reconstituting cell biology’, guest edited by Manuel Théry. Click here for more information.
Opinion – The triple helix of collagens
In a new Opinion article, Billy G. Hudson and colleagues argue that the triple helix is an ancient protein structure of fundamental importance in building the extracellular matrix that enabled animal multicellularity and tissue evolution.
JCS Meeting – Cell dynamics: organelle-cytoskeleton interface
The second in our series of cell dynamics meetings now turns to organelles. This May 2019 meeting in Lisbon, Portugal, aims to bring together scientists studying the interface between organelles and the cytoskeleton at different scales and perspectives using a range of model systems. Find out more and register your interest here.
Review – Dynamics of cortical domains in early Drosophila development
Cortical domains are a central feature of epithelial and polarised cells. Anja Schmidt and Jörg Grosshans present a Review of the dynamics of cortical domains in early Drosophila embryos and discuss underlying mechanisms for formation of cortical domains.
Cell scientist to watch – 2018 Hooke medal winner Andrew McAinsh
“…identify an interesting, good scientific question and try to answer it.”
Andrew McAinsh, Head of Division of Biomedical Sciences at Warwick Medical School, is interested in understanding how the chromosomal multi-protein complex, the kinetochore, ensures error-free chromosome segregation. He is the recipient of the 2018 Hooke medal, established to recognize an emerging leader in cell biology.
We also feature interviews with first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Check out our recent First Person interviews with Thibault Courtheoux and Alghassimou Diallo, Francesco Consolato and Emily Herman.
Articles of interest in our sister journals
Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1
Hyeyoon Lee, Seong-Moon Cheong, Wonhee Han, Youngmu Koo, Saet-Byeol Jo, Gun-Sik Cho, Jae-Seong Yang, Sanguk Kim, Jin-Kwan Han. Development 2018 145: dev143107
PUF-8 facilitates homologous chromosome pairing by promoting proteasome activity during meiotic entry in C. elegans
Ganga Anil Kumar, Kuppuswamy Subramaniam. Development 2018 145: dev163949