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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
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

Actinomycin D

Treat with DTT

Treat with both


3’ fragment

5’ fragment


Conclusions
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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