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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
slide6
No treatment

Actinomycin D

Treat with DTT

Treat with both

slide7
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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