PT  - JOURNAL ARTICLE
AU  - Justin Rendleman
AU  - Zhe Cheng
AU  - Shuvadeep Maity
AU  - Nicolai Kastelic
AU  - Mathias Munschauer
AU  - Kristina Allgoewer
AU  - Guoshou Teo
AU  - Yun Bin Zhang
AU  - Amy Lei
AU  - Brian Parker
AU  - Markus Landthaler
AU  - Lindsay Freeberg
AU  - Scott Kuersten
AU  - Hyungwon Choi
AU  - Christine Vogel
TI  - Quantifying multi-layered expression regulation in response to stress of the endoplasmic reticulum
AID  - 10.1101/308379
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 308379
4099  - http://biorxiv.org/content/early/2018/04/25/308379.short
4100  - http://biorxiv.org/content/early/2018/04/25/308379.full
AB  - 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.