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Quantifying multi-layered expression regulation in response to stress of the endoplasmic reticulum

Item Type:Preprint
Title:Quantifying multi-layered expression regulation in response to stress of the endoplasmic reticulum
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. and Lei, A. and Parker, B. and Landthaler, M. and Freeberg, L. and Kuersten, S. and Choi, H. and Vogel, C.
Abstract:The mammalian response to endoplasmic reticulum (ER) stress dynamically affects all layers of gene expression regulation. We quantified transcript and protein abundance along with footprints of ribosomes and non-ribosomal proteins for thousands of genes in cervical cancer cells responding to treatment with tunicamycin or hydrogen peroxide over an eight hour time course. We identify shared and stress-specific significant regulatory events at the transcriptional and post-transcriptional level and at different phases of the experiment. ER stress regulators increase transcription and translation at different times supporting an adaptive response. ER stress also induces translation of genes from serine biosynthesis and one-carbon metabolism indicating a shift in energy production. Discordant regulation of DNA repair genes suggests transcriptional priming in which delayed translation fine-tunes the early change in the transcriptome. Finally, case studies on stress-dependent alternative splicing and protein-mRNA binding demonstrate the ability of this resource to generate hypotheses for new regulatory mechanisms.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:308379
Date:25 April 2018
Official Publication:https://doi.org/10.1101/308379

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