Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish
- Kyoto University, Japan
- Ryukoku University, Japan
- Osaka University, Japan
- National Institute for Basic Biology, Japan
Abstract
When activated by the accumulation of unfolded proteins in the endoplasmic reticulum, metazoan IRE1, the most evolutionarily conserved unfolded protein response (UPR) transducer, initiates unconventional splicing of XBP1 mRNA. Unspliced and spliced mRNA are translated to produce pXBP1(U) and pXBP1(S), respectively. pXBP1(S) functions as a potent transcription factor, whereas pXBP1(U) targets pXBP1(S) to degradation. In addition, activated IRE1 transmits two signaling outputs independent of XBP1, namely activation of the JNK pathway, which is initiated by binding of the adaptor TRAF2 to phosphorylated IRE1, and regulated IRE1-dependent decay (RIDD) of various mRNAs in a relatively nonspecific manner. Here, we conducted comprehensive and systematic genetic analyses of the IRE1-XBP1 branch of the UPR using medaka fish and found that the defects observed in XBP1-knockout or IRE1-knockout medaka were fully rescued by constitutive expression of pXBP1(S). Thus, the JNK and RIDD pathways are not required for the normal growth and development of medaka.
Data availability
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tokiro-0001Publicly available at the DDBJ (accession no: DRA006141).
Article and author information
Author details
Funding
Ministry of Education, Culture, Sports, Science, and Technology (26291040)
- Kazutoshi Mori
Ministry of Education, Culture, Sports, Science, and Technology (15K18529)
- Tokiro Ishikawa
Ministry of Education, Culture, Sports, Science, and Technology (17H01432)
- Kazutoshi Mori
Ministry of Education, Culture, Sports, Science, and Technology (17K15116)
- Tokiro Ishikawa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in accordance with the guidelines and regulations established by the Animal Research Committee of Kyoto University (approval number: H2819).
Copyright
© 2017, Ishikawa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish
eLife 6:e26845.
https://doi.org/10.7554/eLife.26845
