1. Cell Biology
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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

  1. Tokiro Ishikawa
  2. Makoto Kashima
  3. Atsushi J Nagano
  4. Tomoko Ishikawa-Fujiwara
  5. Yasuhiro Kamei
  6. Takeshi Todo
  7. Kazutoshi Mori  Is a corresponding author
  1. Kyoto University, Japan
  2. Ryukoku University, Japan
  3. Osaka University, Japan
  4. National Institute for Basic Biology, Japan
Research Article
  • Cited 19
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Cite this article as: eLife 2017;6:e26845 doi: 10.7554/eLife.26845

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

The following data sets were generated
    1. Ishikawa T
    2. Mori. K
    (2017) tokiro-0001
    Publicly available at the DDBJ (accession no: DRA006141).

Article and author information

Author details

  1. Tokiro Ishikawa

    Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1718-6764
  2. Makoto Kashima

    Research Institute for Food and Agriculture, Ryukoku University, Otsu, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Atsushi J Nagano

    Faculty of Agriculture, Ryukoku University, Otsu, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Tomoko Ishikawa-Fujiwara

    Graduate School of Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yasuhiro Kamei

    Spectrography and Bioimaging Facility, National Institute for Basic Biology, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Takeshi Todo

    Graduate School of Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Kazutoshi Mori

    Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan
    For correspondence
    mori@upr.biophys.kyoto-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7378-4019

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).

Reviewing Editor

  1. Ramanujan S Hegde, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: March 15, 2017
  2. Accepted: September 25, 2017
  3. Accepted Manuscript published: September 27, 2017 (version 1)
  4. Version of Record published: October 11, 2017 (version 2)
  5. Version of Record updated: October 20, 2017 (version 3)

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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