New insights into the cellular temporal response to proteostatic stress
- New York University, United States
- Berlin Institute for Medical Systems Biology, Germany
- Illumina, Inc, United States
- National University Singapore, Singapore
- Cited 12
- Views 4,386
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Abstract
Maintaining a healthy proteome involves all layers of gene expression regulation. By quantifying temporal changes of the transcriptome, translatome, proteome, and RNA-protein interactome in cervical cancer cells, we systematically characterize the molecular landscape in response to proteostatic challenges. We identify shared and specific responses to misfolded proteins and to oxidative stress, two conditions that are tightly linked. We reveal new aspects of the unfolded protein response, including many genes that escape global translation shutdown. A subset of these genes supports rerouting of energy production in the mitochondria. We also find that many genes change at multiple levels, in either the same or opposing directions, and at different time points. We highlight a variety of putative regulatory pathways, including the stress-dependent alternative splicing of aminoacyl-tRNA synthetases, and protein-RNA binding within the 3' untranslated region of molecular chaperones. These results illustrate the potential of this information-rich resource.
Article and author information
Author details
Funding
National Institutes of Health (1R01GM113237-01)
- Justin Rendleman
- Zhe Cheng
- Shuvadeep Maity
- Guoshou Teo
- Christine Vogel
National Institutes of Health (1R35GM127089-01)
- Justin Rendleman
- Shuvadeep Maity
- Christine Vogel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Juan Valcárcel, Centre de Regulació Genòmica (CRG), Barcelona, Spain
Publication history
- Received: June 8, 2018
- Accepted: September 28, 2018
- Accepted Manuscript published: October 1, 2018 (version 1)
- Version of Record published: October 12, 2018 (version 2)
Copyright
© 2018, Rendleman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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