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New insights into the cellular temporal response to proteostatic stress

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Item Type:Article
Title:New insights into the cellular temporal response to proteostatic stress
Creators Name:Rendleman, J. and Cheng, Z. and Maity, S. and Kastelic, N. and Munschauer, M. and Allgoewer, K. and Teo, G. and Zhang, Y.B.M. and Lei, A. and Parker, B. and Landthaler, M. and Freeberg, L. and Kuersten, S. and Choi, H. and Vogel, C.
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.
Keywords:Amino Acyl-tRNA Synthetases, DNA Repair, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Essential Genes, Eukaryotic Initiation Factor-2, Gene Expression Regulation, HeLa Cells, Membrane Proteins, Nucleic Acid Conformation, Open Reading Frames, Physiological Stress, Principal Component Analysis, Protein Biosynthesis, Proteostasis, Ribosomes, Signal Transduction, Time Factors, Genetic Transcription, Tunicamycin, Unfolded Protein Response, eIF-2 Kinase
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications
Volume:7
Page Range:e39054
Date:12 October 2018
Official Publication:https://doi.org/10.7554/eLife.39054
PubMed:View item in PubMed

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