IRE1alpha hydrolyzes Xbp1 mRNA and Xbp1 mRNA is spliced

Stable Identifier
Reaction [omitted]
Homo sapiens
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Phosphorylated IRE1-alpha homodimers with bound ADP have endoribonuclease activity in their C-terminal (cytosolic) regions. The IRE1-alpha homodimers cleave an internal 26 nucleotide segment out of the Xbp-1 mRNA. In yeast the resulting RNAs are ligated by a tRNA ligase but the corresponding human ligase has not been identified. The cleavage and ligation leads to a frameshift in the Xbp-1 mRNA which results in a longer ORF that encodes Xbp-1 (S), the active form of the Xbp-1 transcription factor

Literature References
PubMed ID Title Journal Year
11779464 XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor

Mori, K, Yamamoto, A, Yoshida, H, Matsui, T, Okada, T

Cell 2001
17026957 Analysis of the XBP1 splicing mechanism using endoplasmic reticulum stress-indicators

Iwawaki, T, Akai, R

Biochem Biophys Res Commun 2006
18242182 RNase domains determine the functional difference between IRE1alpha and IRE1beta

Hosoda, A, Sasaka, S, Imagawa, Y, Tsuru, A, Kohno, K

FEBS Lett 2008
19622636 Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response

Mori, K, Yoshida, H, Oku, M, Uemura, A

J Cell Sci 2009
Catalyst Activity

endoribonuclease activity of p-S724-IRE1 dimer:ADP [endoplasmic reticulum membrane]

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