Defects in IRE1 enhance cell death and fail to degrade mRNAs encoding secretory pathway proteins in the Arabidopsis unfolded protein response

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 14; pp. 5713 - 5718
• Main Authors: Mishiba, Kei-ichiro, Nagashima, Yukihiro, Suzuki, Eiji, Hayashi, Noriko, Ogata, Yoshiyuki, Shimada, Yukihisa, Koizumi, Nozomu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.04.2013; National Acad Sciences
• Subjects: Apoptosis; Arabidopsis - genetics; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; Biodegradation; Biological Sciences; Cell death; Computational Biology; Cytoplasm; DNA Fragmentation; Endoplasmic Reticulum Stress - physiology; Eukaryotes; Evans Blue; Flowers & plants; Gene expression regulation; Gene Expression Regulation, Plant - drug effects; Gene Expression Regulation, Plant - genetics; Genes; Messenger RNA; Microarray Analysis; Mutation - genetics; Plant cells; Protein Kinases - genetics; Protein Kinases - metabolism; Proteins; Ribonucleic acid; RNA; RNA Stability - physiology; Secretory pathway; Seedlings; Splicing; Tunicamycin - pharmacology; Unfolded protein response; Unfolded Protein Response - genetics; Unfolded Protein Response - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1219047110

The unfolded protein response (UPR) is a cellular response highly conserved in eukaryotes to obviate accumulation of misfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) catalyzes the cytoplasmic splicing of mRNA encoding bZIP transcription factors to activate the UPR signaling pathway. Arabidopsis IRE1 was recently shown to be involved in the cytoplasmic splicing of bZIP60 mRNA. In the present study, we demonstrated that an Arabidopsis mutant with defects in two IRE1 paralogs showed enhanced cell death upon ER stress compared with a mutant with defects in bZIP60 and wild type, suggesting an alternative function of IRE1 in the UPR. Analysis of our previous microarray data and subsequent quantitative PCR indicated degradation of mRNAs encoding secretory pathway proteins by tunicamycin, DTT, and heat in an IRE1-dependent manner. The degradation of mRNAs localized to the ER during the UPR was considered analogous to a molecular mechanism referred to as the regulated IRE1-dependent decay of mRNAs reported in metazoans. Another microarray analysis conducted in the condition repressing transcription with actinomycin D and a subsequent Gene Set Enrichment Analysis revealed the regulated IRE1-dependent decay of mRNAs-mediated degradation of a significant portion of mRNAs encoding the secretory pathway proteins. In the mutant with defects in IRE1, genes involved in the cytosolic protein response such as heat shock factor A2 were upregulated by tunicamycin, indicating the connection between the UPR and the cytosolic protein response.