Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish
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...
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| Format: | Article |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/26845 |
| _version_ | 1811200628173570048 |
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| author | Tokiro Ishikawa Makoto Kashima Atsushi J Nagano Tomoko Ishikawa-Fujiwara Yasuhiro Kamei Takeshi Todo Kazutoshi Mori |
| author_facet | Tokiro Ishikawa Makoto Kashima Atsushi J Nagano Tomoko Ishikawa-Fujiwara Yasuhiro Kamei Takeshi Todo Kazutoshi Mori |
| author_sort | Tokiro Ishikawa |
| collection | DOAJ |
| description | 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. The unfolded protein response sensor/transducer IRE1-mediated splicing of XBP1 mRNA encoding its active downstream transcription factor to maintain the homeostasis of the endoplasmic reticulum is sufficient for growth and development of medaka fish. |
| first_indexed | 2024-04-12T02:06:47Z |
| format | Article |
| id | doaj.art-46bf4fdf763e447b9aef8609169b5b93 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:06:47Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-46bf4fdf763e447b9aef8609169b5b932022-12-22T03:52:30ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.26845Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fishTokiro Ishikawa0https://orcid.org/0000-0003-1718-6764Makoto Kashima1Atsushi J Nagano2Tomoko Ishikawa-Fujiwara3Yasuhiro Kamei4Takeshi Todo5Kazutoshi Mori6https://orcid.org/0000-0001-7378-4019Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, JapanResearch Institute for Food and Agriculture, Ryukoku University, Otsu, JapanFaculty of Agriculture, Ryukoku University, Otsu, JapanGraduate School of Medicine, Osaka University, Suita, JapanSpectrography and Bioimaging Facility, National Institute for Basic Biology, Okazaki, JapanGraduate School of Medicine, Osaka University, Suita, JapanDepartment of Biophysics, Graduate School of Science, Kyoto University, Kyoto, JapanWhen 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. The unfolded protein response sensor/transducer IRE1-mediated splicing of XBP1 mRNA encoding its active downstream transcription factor to maintain the homeostasis of the endoplasmic reticulum is sufficient for growth and development of medaka fish.https://elifesciences.org/articles/26845protein foldingendoplasmic reticulummolecular chaperonemRNA splicingcell deathOryzias latipes |
| spellingShingle | Tokiro Ishikawa Makoto Kashima Atsushi J Nagano Tomoko Ishikawa-Fujiwara Yasuhiro Kamei Takeshi Todo Kazutoshi Mori Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish eLife protein folding endoplasmic reticulum molecular chaperone mRNA splicing cell death Oryzias latipes |
| title | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
| title_full | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
| title_fullStr | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
| title_full_unstemmed | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
| title_short | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
| title_sort | unfolded protein response transducer ire1 mediated signaling independent of xbp1 mrna splicing is not required for growth and development of medaka fish |
| topic | protein folding endoplasmic reticulum molecular chaperone mRNA splicing cell death Oryzias latipes |
| url | https://elifesciences.org/articles/26845 |
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