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
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.
Data availability
The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (Barrett et al., 2013; Edgar et al., 2002) and are accessible through GEO Series accession number GSE113171. The mass spectrometry data including the MaxQuant output files have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaíno et al., 2016) partner repository with the dataset identifier PXD008575.
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The Unfolded Protein Response Triggers Selective mRNA Release from the Endoplasmic Reticulumhttps://www.sciencedirect.com/science/article/pii/S0092867414010435?via%3Dihub#dtbox1.
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Landscape and variation of RNA secondary structure across the human transcriptomePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE50676).
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A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE72681).
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
Version 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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New insights into the cellular temporal response to proteostatic stress
eLife 7:e39054.
https://doi.org/10.7554/eLife.39054
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