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Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
The 5′ cap structures of higher eukaryote mRNAs have ribose 2′-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2′-O-methylation of mRNA remains elusive....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182538/ https://www.ncbi.nlm.nih.gov/pubmed/21217758 http://dx.doi.org/10.1038/ni.1979 |
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author | Züst, Roland Cervantes-Barragan, Luisa Habjan, Matthias Maier, Reinhard Neuman, Benjamin W Ziebuhr, John Szretter, Kristy J Baker, Susan C Barchet, Winfried Diamond, Michael S Siddell, Stuart G Ludewig, Burkhard Thiel, Volker |
author_facet | Züst, Roland Cervantes-Barragan, Luisa Habjan, Matthias Maier, Reinhard Neuman, Benjamin W Ziebuhr, John Szretter, Kristy J Baker, Susan C Barchet, Winfried Diamond, Michael S Siddell, Stuart G Ludewig, Burkhard Thiel, Volker |
author_sort | Züst, Roland |
collection | PubMed |
description | The 5′ cap structures of higher eukaryote mRNAs have ribose 2′-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2′-O-methylation of mRNA remains elusive. Here we show that 2′-O-methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2′-O-methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2′-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2′-O-methylation of mRNA suggests that RNA modifications such as 2′-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3182538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-31825382011-09-29 Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 Züst, Roland Cervantes-Barragan, Luisa Habjan, Matthias Maier, Reinhard Neuman, Benjamin W Ziebuhr, John Szretter, Kristy J Baker, Susan C Barchet, Winfried Diamond, Michael S Siddell, Stuart G Ludewig, Burkhard Thiel, Volker Nat Immunol Article The 5′ cap structures of higher eukaryote mRNAs have ribose 2′-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2′-O-methylation of mRNA remains elusive. Here we show that 2′-O-methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2′-O-methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2′-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2′-O-methylation of mRNA suggests that RNA modifications such as 2′-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users. Nature Publishing Group US 2011-01-09 2011 /pmc/articles/PMC3182538/ /pubmed/21217758 http://dx.doi.org/10.1038/ni.1979 Text en © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2011 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Article Züst, Roland Cervantes-Barragan, Luisa Habjan, Matthias Maier, Reinhard Neuman, Benjamin W Ziebuhr, John Szretter, Kristy J Baker, Susan C Barchet, Winfried Diamond, Michael S Siddell, Stuart G Ludewig, Burkhard Thiel, Volker Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title | Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title_full | Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title_fullStr | Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title_full_unstemmed | Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title_short | Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 |
title_sort | ribose 2′-o-methylation provides a molecular signature for the distinction of self and non-self mrna dependent on the rna sensor mda5 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182538/ https://www.ncbi.nlm.nih.gov/pubmed/21217758 http://dx.doi.org/10.1038/ni.1979 |
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