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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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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. |
format | Text |
id | pubmed-2728407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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