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A role for the ribosome-associated complex in activation of the IRE1 branch of UPR

ABSTRACT: The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and the decoding center, a position prime for sensing and coordinating translation and folding. Loss of RAC is known to result in growth defects and sensitization to translational and osmotic stresses. However, the physiological substrates of RAC and the mechanism(s) by which RAC is involved in responding to specific stresses in higher eukaryotes remain obscure. Data presented here uncover an essential function of mammalian RAC in the unfolded protein response (UPR). Knockdown of RAC sensitizes mammalian cells to ER stress and selectively interferes with IRE1 branch activation. Higher-order oligomerization of the IRE1α kinase/endoribonuclease depends upon RAC. These results reveal a surveillance function for RAC in the UPR: modulating IRE1α clustering as required for endonuclease activation and splicing of the substrate Xbp1 mRNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173852 | GEO | 2021/06/14

REPOSITORIES: GEO

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The IRE1 interactome in human LS174T colon epithelial cells

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A role for the ribosome-associated complex in activation of the IRE1 branch of UPR.

Project description:The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and the decoding center, a position prime for sensing and coordinating translation and folding. Loss of RAC is known to result in growth defects and sensitization to translational and osmotic stresses. However, the physiological substrates of RAC and the mechanism(s) by which RAC is involved in responding to specific stresses in higher eukaryotes remain obscure. The data presented here uncover an essential function of mammalian RAC in the unfolded protein response (UPR). Knockdown of RAC sensitizes mammalian cells to endoplasmic reticulum (ER) stress and selectively interferes with IRE1 branch activation. Higher-order oligomerization of the inositol-requiring enzyme 1α (IRE1α) kinase/endoribonuclease depends upon RAC. These results reveal a surveillance function for RAC in the UPR, as follows: modulating IRE1α clustering as required for endonuclease activation and splicing of the substrate Xbp1 mRNA.

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A role for the ribosome-associated complex in activation of the IRE1 branch of UPR.

Project description: Not available

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A role for the ribosome-associated complex in activation of the IRE1 branch of UPR

Project description:A role for the ribosome-associated complex in activation of the IRE1 branch of UPR

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The UPR branch IRE1-bZIP60 in plants plays an essential role in viral infection and is complementary to the only UPR pathway in yeast.

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