2014年11月6日 · IRE1, an endoplasmic reticulum (ER) kinase/RNase, splices XBP1/HAC1 to produce an active transcription factor but also cleaves ER-associated mRNA through regulated IRE1-dependent decay (RIDD). Using biochemical studies, Tam et al. demonstrate that cleavage of XBP1 and HAC1 and RIDD are distinct and separable activities.

2025年3月4日 · In the UPR signaling pathway, HAC1 mRNA in budding yeast 32,33,34 or XBP1 mRNA in metazoans 32,33,34 is targeted to the ER-resident protein kinase and endonuclease Ire1 32,35,36.

2001年12月28日 · HAC1 mRNA encodes the basic leucine zipper (bZIP)-type transcription factor Hac1p, which directly activates transcription of UPR target genes. Hac1p is synthesized only after Ire1p-mediated splicing occurs because the HAC1 intron has a strong ability to block translation.

Here, we summarize various approaches to study the IRE1-Hac1 pathway in yeast and the homologous IRE1-XBP1 pathway in mammalian cells. We present microbiological growth assays for the UPR, reporter assays for UPR signaling, direct techniques to measure UPR activation in vivo, methods to study translation of HAC1 mRNA, and in vitro cleavage and ...

2014年11月6日 · 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 regulate …

2022年3月24日 · We show that Pumilio protects Drosophila Xbp1 against RIDD, without perturbing canonical Ire1-driven Xbp1 splicing. Furthermore, we provide evidence that Ire1 phosphorylates Pumilio under ER...

2005年4月1日 · In the following report, we describe a variety of methods used to arrive at our current understanding of yeast IRE1-dependent HAC1 splicing and mammalian IRE1α-dependent XBP1 splicing, with focus on recently developed methods for detecting and measuring HAC1 or XBP1 mRNA splicing from in vitro or in vivo systems.

2001年12月28日 · In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR).

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 ...

2014年11月6日 · Using in vitro experiments, we found that IRE1 has two different modes of action: is cleaved XBP1/HAC1 by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity.