In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-09-27)
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. 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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.26845.001
DOI:
10.7554/eLife.26845.002
DOI:
10.7554/eLife.26845.003
DOI:
10.7554/eLife.26845.004
DOI:
10.7554/eLife.26845.005
DOI:
10.7554/eLife.26845.006
DOI:
10.7554/eLife.26845.007
DOI:
10.7554/eLife.26845.008
DOI:
10.7554/eLife.26845.009
DOI:
10.7554/eLife.26845.010
DOI:
10.7554/eLife.26845.011
DOI:
10.7554/eLife.26845.012
DOI:
10.7554/eLife.26845.013
DOI:
10.7554/eLife.26845.014
DOI:
10.7554/eLife.26845.017
DOI:
10.7554/eLife.26845.018
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
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