The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis.
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.
Department of Biochemistry and Biophysics ,  University of California, San Francisco ,  San Francisco ,  United States.
Philipp
P
Kimmig
Marcy
M
Diaz
Jiashun
J
Zheng
Christopher C
CC
Williams
Alexander
A
Lang
Tomas
T
Aragón
Hao
H
Li
Peter
P
Walter
D020413:3' Untranslated Regions; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D014176:Protein Biosynthesis; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D056811:Unfolded Protein Response
D020413:3' Untranslated Regions; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases