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.
Keywords: ER stress, unfolded protein response (UPR), mRNA stability, Transcription Factors, gene regulatory networks (GRN)
Citation: Arensdorf AM, Diedrichs D and Rutkowski DT (2013) Regulation of the transcriptome by ER stress: non-canonical mechanisms and physiological consequences. Front. Genet. 4:256. doi: 10.3389/fgene.2013.00256
Received: 24 September 2013; Accepted: 08 November 2013;
Published online: 02 December 2013.
Edited by:Kezhong Zhang, Wayne State University, USA
Copyright © 2013 Arensdorf, Diedrichs and Rutkowski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: D. Thomas Rutkowski, Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, 51 Newton Rd., Iowa City, 52242 IA, USA e-mail: email@example.com