Journal
EMBO REPORTS
Volume 16, Issue 12, Pages 1688-1698Publisher
WILEY-BLACKWELL
DOI: 10.15252/embr.201540955
Keywords
endoribonuclease; ER stress; RNA conformational change; unfolded protein response; XBP1 splicing
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Funding
- Long-Term Postdoctoral Fellowship, Human Frontiers Science Program
- Irvington Postdoctoral Fellowship of the Cancer Research Institute
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The kinase/endonuclease IRE1 is the most conserved signal transducer of the unfolded protein response (UPR), an intracellular signaling network that monitors and regulates the protein folding capacity of the endoplasmic reticulum (ER). Upon sensing protein folding perturbations in the ER, IRE1 initiates the unconventional splicing of XBP1 mRNA culminating in the production of the transcription factor XBP1s, which expands the ER's protein folding capacity. We show that an RNA-intrinsic conformational change causes the intron of XBP1 mRNA to be ejected and the exons to zipper up into an extended stem, juxtaposing the RNA ends for ligation. These conformational rearrangements are important for XBP1 mRNA splicing in vivo. The features that point to such active participation of XBP1 mRNA in the splicing reaction are highly conserved throughout metazoan evolution, supporting their importance in orchestrating XBP1 mRNA processing with efficiency and fidelity.
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