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Major Claims

Major Claims. IRE1 initiates an XBP-1 independent pathway during the unfolding protein response IRE1 nuclease has a broader range of substrates than XBP-1 IRE1 mediates the rapid degradation of a subset of mRNA Degradation is dependent on ER localization and peptide sequence. No treatment.

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Major Claims

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Presentation Transcript

  1. Major Claims • IRE1 initiates an XBP-1 independent pathway during the unfolding protein response • IRE1 nuclease has a broader range of substrates than XBP-1 • IRE1 mediates the rapid degradation of a subset of mRNA • Degradation is dependent on ER localization and peptide sequence

  2. No treatment Actinomycin D Treat with DTT Treat with both

  3. 3’ fragment 5’ fragment

  4. Conclusions • IRE1 mediates repression of ER targeted mRNA • Repression is due to mRNA stability not transcription • Cleavage of mRNA initiates degradation • mRNA decay requires cotranslational translocation and translation of the correct peptide

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