IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA - PubMed

Affiliations

• PMID: 11780124
• DOI: 10.1038/415092a

IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA

Marcella Calfon et al. Nature. 2002.

Erratum in

• Nature 2002 Nov 14;420(6912):202

Abstract

The unfolded protein response (UPR), caused by stress, matches the folding capacity of endoplasmic reticulum (ER) to the load of client proteins in the organelle. In yeast, processing of HAC1 mRNA by activated Ire1 leads to synthesis of the transcription factor Hac1 and activation of the UPR. The responses to activated IRE1 in metazoans are less well understood. Here we demonstrate that mutations in either ire-1 or the transcription-factor-encoding xbp-1 gene abolished the UPR in Caenorhabditis elegans. Mammalian XBP-1 is essential for immunoglobulin secretion and development of plasma cells, and high levels of XBP-1 messenger RNA are found in specialized secretory cells. Activation of the UPR causes IRE1-dependent splicing of a small intron from the XBP-1 mRNA both in C. elegans and mice. The protein encoded by the processed murine XBP-1 mRNA accumulated during the UPR, whereas the protein encoded by unprocessed mRNA did not. Purified mouse IRE1 accurately cleaved XBP-1 mRNA in vitro, indicating that XBP-1 mRNA is a direct target of IRE1 endonucleolytic activity. Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes.

Comment in

• The biological meaning of the UPR.

  Hetz C. Hetz C. Nat Rev Mol Cell Biol. 2013 Jul;14(7):404. doi: 10.1038/nrm3606. Epub 2013 Jun 12. Nat Rev Mol Cell Biol. 2013. PMID: 23756618 No abstract available.

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