Ire1 has distinct catalytic mechanisms for XBP1/HAC1 splicing and RIDD.

ABSTRACT: An evolutionarily conserved unfolded protein response (UPR) component, IRE1, cleaves XBP1/HAC1 introns in order to generate spliced mRNAs that are translated into potent transcription factors. IRE1 also cleaves endoplasmic-reticulum-associated RNAs leading to their decay, an activity termed regulated IRE1-dependent decay (RIDD); however, the mechanism by which IRE1 differentiates intron cleavage from RIDD is not well understood. Using in vitro experiments, we found that IRE1 has two different modes of action: XBP1/HAC1 is cleaved by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity. Furthermore, these distinct activities can be separated by complementation of catalytically inactive IRE1 RNase and mutations at olig

SUBMITTER: Tam AB 

PROVIDER: S-EPMC4486022 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature