The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis

• Published in: eLife Vol. 1; p. e00048
• Main Authors: Kimmig, Philipp, Diaz, Marcy, Zheng, Jiashun, Williams, Christopher C, Lang, Alexander, Aragón, Tomas, Li, Hao, Walter, Peter
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 15.10.2012; eLife Sciences Publications, Ltd
• Subjects: 3' Untranslated Regions; Biochemistry; Biophysics; Bip1 mRNA stabilization; Cell Biology; Collaboration; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; ER homeostasis; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal; Genes; Homeostasis; Homeostasis - genetics; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Ire1; Kinases; Physiology; Protein Biosynthesis; Protein Folding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Regression analysis; RNA Splicing; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; selective mRNA decay; Signal Transduction; Splicing; Transcription factors; Transcription, Genetic; Unfolded Protein Response; Yeast; Bip1 mRNA stabilization; selective mRNA decay; ER homeostasis; Unfolded Protein Response; S. pombe; Ire1
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.00048

The unfolded protein response (UPR) monitors the protein folding capacity of the endoplasmic reticulum (ER). In all organisms analyzed to date, the UPR drives transcriptional programs that allow cells to cope with ER stress. The non-conventional splicing of Hac1 (yeasts) and XBP1 (metazoans) mRNA, encoding orthologous UPR transcription activators, is conserved and dependent on Ire1, an ER membrane-resident kinase/endoribonuclease. We found that the fission yeast Schizosaccharomyces pombe lacks both a Hac1/XBP1 ortholog and a UPR-dependent-transcriptional-program. Instead, Ire1 initiates the selective decay of a subset of ER-localized-mRNAs that is required to survive ER stress. We identified Bip1 mRNA, encoding a major ER-chaperone, as the sole mRNA cleaved upon Ire1 activation that escapes decay. Instead, truncation of its 3' UTR, including loss of its polyA tail, stabilized Bip1 mRNA, resulting in increased Bip1 translation. Thus, S. pombe uses a universally conserved stress-sensing machinery in novel ways to maintain homeostasis in the ER.DOI:http://dx.doi.org/10.7554/eLife.00048.001.