Regulated Ire1-dependent decay of messenger RNAs in mammalian cells

By J. Hollien, Jonathan H. Lin, Han Li, Nicole Stevens, Peter Walter, Jonathan S. Weissman. Journal of Cell Biology, 2009

1,010 citations recorded by the source corpus.

Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER. The cytoplasmic nuclease domain of Ire1 cleaves the messenger RNA (mRNA) encoding XBP-1 (X-box–binding protein 1), enabling splicing and production of this active transcription factor. We recently showed that Ire1 activation independently induces the rapid turnover of mRNAs encoding membrane and secreted proteins in Drosophila melanogaster cells through a pathway we call regulated Ire1-dependent decay (RIDD). In this study, we show that mouse fibroblasts expressing wild-type Ire1 but not an Ire1 variant lacking nuclease activity also degrade mRNAs in response to ER stress. Using a second variant of Ire1 that is activated by a small adenosine triphosphate analogue, we show that although XBP-1 splicing can be artificially induced in the absence of ER stress, RIDD appears to require both Ire1 activity and ER stress. Our data suggest that cells use a multitiered mechanism by which different conditions in the ER lead to distinct outputs from Ire1.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5322d3b9f5ee17d5b931f0c32173125d6a7304ed

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Citations in the corpus

Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease (2010, neutral): “These mRNAs are degraded by IRE1, thereby preventing their translation, an additional measure to relieve ER stress (Hollien et al., 2009; Hollien and Weissman, 2006).”
The impact of the unfolded protein response on human disease (2012, background): “It was also reported that IRE1 indiscriminately degrades ER-localized mRNAs that can lead to cell death (Hollien et al., 2009; Vecchi et al., 2009).”
Measuring ER stress and the unfolded protein response using mammalian tissue culture system (2011, background): “This is largely dependent on the RNase activity of IRE1a (Hollien and Weissman, 2006; Hollien et al., 2009).”
Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. (2018, background): “specificity to degrade many other ER-bound mRNAs, including itself, at both stem-loop and non-stemloop sites, through regulated IRE1α-dependent decay (RIDD)(19-21).”
Endoplasmic Reticulum Stress and Associated ROS (2016, background): “To reduce the entry of additional unfolded proteins, the active RNAase can also cleave ER-localized messages leading, to degradation [12–14].”
Regulation of cytoplasmic mRNA decay (2012, neutral): “IRE1 also cleaves and destabilizes mRNAs encoding some of the proteins that transit through the endoplasmic reticulum (that is, membrane-bound and secreted proteins”
Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer (2017, neutral): “However, under severe ER stress, IRE1α can also oligomerize and sequence-specifically degrade multiple ER-localized mRNAs and microRNAs in a pro-apoptotic process known as regulated IRE1α-dependent decay (RIDD) (Hollien et al., 2009; Lerner et al., 2012).”
ER stress-induced cell death mechanisms. (2013, background): “Recently, regulated IRE1-dependent decay of mRNA (RIDD) was shown to reduce ER localized mRNAs in both insect (Drosophila) and mammalian (mouse) cells [10,11].”
Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress (2011, background): “At higher levels of stress signalling, however, there is evidence in cultured cells that IRE1 may contribute to rather promiscuous degradation of membrane-associated mRNAs through a process referred to as regulated IRE1 dependent decay or RID”
The unfolded protein response: controlling cell fate decisions under ER stress and beyond (2012, background): “In addition, the selective degradation of mRNA encoding for certain ER-located proteins is initiated through regulated IRE1-dependent decay ( RIDD”
ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis (2015, background): “Expression of known regulated IRE1a-dependent decay (RIDD) target mRNAs (Hetz et al., 2013; Hollien et al., 2009; Osorio et al., 2014) was unchanged betweenWT and XBP1-deficient tDCs (Figure S4C), ruling out IRE1a artificial overactivation due to absence of functional XBP1.”
Endoplasmic reticulum stress sensing in the unfolded protein response. (2013, background): “This pathway, termed Regulated Ire1-Depen- dent Decay (RIDD), cleaves mRNAs encoding membrane and secreted proteins and may consequently decrease the protein influx into the ER.”