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IRE1- and HAC1-independent transcriptional regulation in the unfolded protein response of yeast

Schröder, M.; Clark, R.; Kaufman, R.J.

Authors

R. Clark

R.J. Kaufman



Abstract

The unfolded protein response (UPR) is a signalling pathway leading to transcriptional activation of genes that protect cells from accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). In yeast, the only known ER stress signalling pathway originates at the type I transmembrane protein kinase/endoribonuclease Ire1p. Ire1p regulates synthesis of the basic leucine-zipper (bZIP)-containing transcription factor Hac1p by controlling splicing of HAC1 mRNA. Only spliced HAC1 mRNA (HAC1i) is translated, and Hac1ip activates transcription of genes that contain a conserved UPR element (UPRE) in their promoters. Here, we demonstrate that in addition to this well-understood ER stress signalling pathway, a second, IRE1, HAC1 and UPRE-independent mechanism for transcriptional activation upon ER stress, exists in yeast. A genetic screen identified recessive SIN4 alleles as suppressors of a defective UPR in ire1D strains. Elevation of basal transcription in sin4 strains or by tethering the RNA polymerase II holoenzyme with LexAp-holoenzyme component fusion proteins to a promoter allowed for activation of the promoter by ER stress in an IRE1, HAC1 and UPRE-independent manner. We propose that this novel second ER-to-nucleus signal transduction pathway culminates in core promoter activation (CPA) through stimulation of RNA polymerase II holoenzyme activity. Core promoter activation was observed upon diverse cellular stresses, suggesting it represents a primordial stress-induced gene activation mechanism.

Citation

Schröder, M., Clark, R., & Kaufman, R. (2003). IRE1- and HAC1-independent transcriptional regulation in the unfolded protein response of yeast. Molecular Microbiology, 49(3), 591-606. https://doi.org/10.1046/j.1365-2958.2003.03585.x

Journal Article Type Article
Publication Date Aug 1, 2003
Deposit Date May 16, 2007
Journal Molecular Microbiology
Print ISSN 0950-382X
Electronic ISSN 1365-2958
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 49
Issue 3
Pages 591-606
DOI https://doi.org/10.1046/j.1365-2958.2003.03585.x
Keywords Unfolded protein response, Yeast, IRE1, HAC1.
Public URL https://durham-repository.worktribe.com/output/1572817
Publisher URL http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2958.2003.03585.x