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Regulated Ire1-dependent decay of messenger RNAs in mammalian cells

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), ena...

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Detalles Bibliográficos
Autores principales: Hollien, Julie, Lin, Jonathan H., Li, Han, Stevens, Nicole, Walter, Peter, Weissman, Jonathan S.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728407/
https://www.ncbi.nlm.nih.gov/pubmed/19651891
http://dx.doi.org/10.1083/jcb.200903014
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author Hollien, Julie
Lin, Jonathan H.
Li, Han
Stevens, Nicole
Walter, Peter
Weissman, Jonathan S.
author_facet Hollien, Julie
Lin, Jonathan H.
Li, Han
Stevens, Nicole
Walter, Peter
Weissman, Jonathan S.
author_sort Hollien, Julie
collection PubMed
description 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.
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spelling pubmed-27284072010-02-10 Regulated Ire1-dependent decay of messenger RNAs in mammalian cells Hollien, Julie Lin, Jonathan H. Li, Han Stevens, Nicole Walter, Peter Weissman, Jonathan S. J Cell Biol Research Articles 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. The Rockefeller University Press 2009-08-10 /pmc/articles/PMC2728407/ /pubmed/19651891 http://dx.doi.org/10.1083/jcb.200903014 Text en © 2009 Hollien et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Hollien, Julie
Lin, Jonathan H.
Li, Han
Stevens, Nicole
Walter, Peter
Weissman, Jonathan S.
Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title_full Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title_fullStr Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title_full_unstemmed Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title_short Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
title_sort regulated ire1-dependent decay of messenger rnas in mammalian cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728407/
https://www.ncbi.nlm.nih.gov/pubmed/19651891
http://dx.doi.org/10.1083/jcb.200903014
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