New insights into the cellular temporal response to proteostatic stress

Justin Rendleman, Zhe Cheng, Shuvadeep Maity, Nicolai Kastelic, Mathias Munschauer, Kristina Allgoewer, Guoshou Teo, Yun Bin Matteo Zhang, Amy Lei, Brian Parker, Markus Landthaler, Lindsay Freeberg, Scott Kuersten, Hyungwon Choi, Christine Vogel

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume7
DOIs
StatePublished - Oct 12 2018

Fingerprint

Genes
Proteome
Gene expression regulation
Unfolded Protein Response
Amino Acyl-tRNA Synthetases
Proteins
Mitochondria
Molecular Chaperones
Oxidative stress
RNA-Binding Proteins
Alternative Splicing
Gene Expression Regulation
3' Untranslated Regions
Transcriptome
Uterine Cervical Neoplasms
Oxidative Stress
Cells
RNA
Direction compound

Keywords

  • central dogma
  • computational biology
  • energy metabolism
  • genetics
  • genomics
  • human
  • proteostasis
  • stress response
  • systems biology
  • translation regulation
  • unfolded protein response

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Rendleman, J., Cheng, Z., Maity, S., Kastelic, N., Munschauer, M., Allgoewer, K., ... Vogel, C. (2018). New insights into the cellular temporal response to proteostatic stress. eLife, 7. https://doi.org/10.7554/eLife.39054

New insights into the cellular temporal response to proteostatic stress. / Rendleman, Justin; Cheng, Zhe; Maity, Shuvadeep; Kastelic, Nicolai; Munschauer, Mathias; Allgoewer, Kristina; Teo, Guoshou; Zhang, Yun Bin Matteo; Lei, Amy; Parker, Brian; Landthaler, Markus; Freeberg, Lindsay; Kuersten, Scott; Choi, Hyungwon; Vogel, Christine.

In: eLife, Vol. 7, 12.10.2018.

Research output: Contribution to journalArticle

Rendleman, J, Cheng, Z, Maity, S, Kastelic, N, Munschauer, M, Allgoewer, K, Teo, G, Zhang, YBM, Lei, A, Parker, B, Landthaler, M, Freeberg, L, Kuersten, S, Choi, H & Vogel, C 2018, 'New insights into the cellular temporal response to proteostatic stress', eLife, vol. 7. https://doi.org/10.7554/eLife.39054
Rendleman J, Cheng Z, Maity S, Kastelic N, Munschauer M, Allgoewer K et al. New insights into the cellular temporal response to proteostatic stress. eLife. 2018 Oct 12;7. https://doi.org/10.7554/eLife.39054
Rendleman, Justin ; Cheng, Zhe ; Maity, Shuvadeep ; Kastelic, Nicolai ; Munschauer, Mathias ; Allgoewer, Kristina ; Teo, Guoshou ; Zhang, Yun Bin Matteo ; Lei, Amy ; Parker, Brian ; Landthaler, Markus ; Freeberg, Lindsay ; Kuersten, Scott ; Choi, Hyungwon ; Vogel, Christine. / New insights into the cellular temporal response to proteostatic stress. In: eLife. 2018 ; Vol. 7.
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