title: Regulation of the transcriptome by ER stress: non-canonical mechanisms and physiological consequences.
abstract: The mammalian unfolded protein response (UPR) is propagated by three ER-resident transmembrane proteins, each of which initiates a signaling cascade that ultimately culminates in production of a transcriptional activator. The UPR was originally characterized as a pathway for upregulating ER chaperones, and a comprehensive body of subsequent work has shown that protein synthesis, folding, oxidation, trafficking, and degradation are all transcriptionally enhanced by the UPR. However, the global reach of the UPR extends to genes involved in diverse physiological processes having seemingly little to do with ER protein folding, and this includes a substantial number of mRNAs that are suppressed by stress rather than stimulated. Through multiple non-canonical mechanisms emanating from each of the UPR pathways, the cell dynamically regulates transcription and mRNA degradation. Here we highlight these mechanisms and their increasingly appreciated impact on physiological processes.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine Iowa City, IA, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Arensdorf
authors.affiliation: Department of Mathematics and Computer Science, Wheaton College Wheaton, IL, USA.
authors.forename: Danilo
authors.initials: D
authors.lastname: Diedrichs
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine Iowa City, IA, USA ; Department of Internal Medicine, University of Iowa Carver College of Medicine Iowa City, IA, USA.
authors.forename: D Thomas
authors.initials: DT
authors.lastname: Rutkowski
keywords: ER stress; Transcription Factors; gene regulatory networks (GRN); mRNA stability; unfolded protein response (UPR)