1. Computational and Systems Biology
  2. Genetics and Genomics
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New insights into the cellular temporal response to proteostatic stress

  1. Justin Rendleman
  2. Zhe Cheng
  3. Shuvadeep Maity
  4. Nicolai Kastelic
  5. Mathias Munschauer
  6. Kristina Allgoewer
  7. Guoshou Teo
  8. Yun Bin Matteo Zhang
  9. Amy Lei
  10. Brian Parker
  11. Markus Landthaler
  12. Lindsay Freeberg
  13. Scott Kuersten
  14. Hyungwon Choi
  15. Christine Vogel  Is a corresponding author
  1. New York University, United States
  2. Berlin Institute for Medical Systems Biology, Germany
  3. Illumina, Inc, United States
  4. National University Singapore, Singapore
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Cite this article as: eLife 2018;7:e39054 doi: 10.7554/eLife.39054

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Justin Rendleman

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8152-7127

  2. Zhe Cheng

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  3. Shuvadeep Maity

    Department of Biology, New York University, New York City, United States
    Competing interests
    No competing interests declared.

  4. Nicolai Kastelic

    Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  5. Mathias Munschauer

    Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  6. Kristina Allgoewer

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  7. Guoshou Teo

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  8. Yun Bin Matteo Zhang

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  9. Amy Lei

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  10. Brian Parker

    Department of Biology, New York University, New York, United States
    Competing interests
    No competing interests declared.

  11. Markus Landthaler

    Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  12. Lindsay Freeberg

    Illumina, Inc, Madison, United States
    Competing interests
    Lindsay Freeberg, affiliated with Illumina Inc. No other competing interests to declare.

  13. Scott Kuersten

    Illumina, Inc, Madison, United States
    Competing interests
    Scott Kuersten, affiliated with Illumina Inc. No other competing interests to declare.

  14. Hyungwon Choi

    National University Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.

  15. Christine Vogel

    Department of Biology, New York University, New York, United States
    For correspondence
    cvogel@nyu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2856-3118

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

  1. Juan Valcárcel, Centre de Regulació Genòmica (CRG), Barcelona, Spain

Publication history

  1. Received: June 8, 2018
  2. Accepted: September 28, 2018
  3. Accepted Manuscript published: October 1, 2018 (version 1)
  4. 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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