Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
Identifieur interne : 001601 ( Main/Exploration ); précédent : 001600; suivant : 001602Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
Auteurs : Roland Züst [Suisse, Singapour] ; Luisa Cervantes-Barragan [Suisse] ; Matthias Habjan [Suisse] ; Reinhard Maier [Suisse] ; Benjamin W. Neuman [Royaume-Uni] ; John Ziebuhr [Royaume-Uni, Allemagne] ; Kristy J. Szretter [États-Unis] ; Susan C. Baker [États-Unis] ; Winfried Barchet [Allemagne] ; Michael S. Diamond [États-Unis] ; Stuart G. Siddell [Royaume-Uni] ; Burkhard Ludewig [Suisse] ; Volker Thiel [Suisse]Source :
- Nature Immunology [ 1529-2908 ] ; 2011-02.
Abstract
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.
The biological role of 2′-O-methylation of host and viral mRNA has remained elusive. Thiel and co-workers show that this modification modulates the induction of type I interferon and sensitivity to interferon.
Url:
DOI: 10.1038/ni.1979
Affiliations:
- Allemagne, Royaume-Uni, Singapour, Suisse, États-Unis
- Canton de Zurich, District de Cologne, Illinois, Missouri (État), Rhénanie-du-Nord-Westphalie
- Bonn, Saint-Louis (Missouri), Zurich
- Université de Zurich, École de médecine (Université Washington de Saint-Louis)
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All Rights Reserved.</publisher><date when="2011-02">2011-02</date><biblScope unit="vol">12</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="137">137</biblScope><biblScope unit="page" to="143">143</biblScope><date type="Copyright" when="2011">2011</date></imprint><idno type="ISSN">1529-2908</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1529-2908</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">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.</div><div type="abstract" xml:lang="eng">The biological role of 2′-O-methylation of host and viral mRNA has remained elusive. Thiel and co-workers show that this modification modulates the induction of type I interferon and sensitivity to interferon.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li><li>Singapour</li><li>Suisse</li><li>États-Unis</li></country><region><li>Canton de Zurich</li><li>District de Cologne</li><li>Illinois</li><li>Missouri (État)</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Bonn</li><li>Saint-Louis (Missouri)</li><li>Zurich</li></settlement><orgName><li>Université de Zurich</li><li>École de médecine (Université Washington de Saint-Louis)</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Zust, Roland" sort="Zust, Roland" uniqKey="Zust R" first="Roland" last="Züst">Roland Züst</name></noRegion><name sortKey="Cervantes Barragan, Luisa" sort="Cervantes Barragan, Luisa" uniqKey="Cervantes Barragan L" first="Luisa" last="Cervantes-Barragan">Luisa Cervantes-Barragan</name><name sortKey="Habjan, Matthias" sort="Habjan, Matthias" uniqKey="Habjan M" first="Matthias" last="Habjan">Matthias Habjan</name><name sortKey="Ludewig, Burkhard" sort="Ludewig, Burkhard" uniqKey="Ludewig B" first="Burkhard" last="Ludewig">Burkhard Ludewig</name><name sortKey="Ludewig, Burkhard" sort="Ludewig, Burkhard" uniqKey="Ludewig B" first="Burkhard" last="Ludewig">Burkhard Ludewig</name><name sortKey="Maier, Reinhard" sort="Maier, Reinhard" uniqKey="Maier R" first="Reinhard" last="Maier">Reinhard Maier</name><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name></country><country name="Singapour"><noRegion><name sortKey="Zust, Roland" sort="Zust, Roland" uniqKey="Zust R" first="Roland" last="Züst">Roland Züst</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Neuman, Benjamin W" sort="Neuman, Benjamin W" uniqKey="Neuman B" first="Benjamin W" last="Neuman">Benjamin W. Neuman</name></noRegion><name sortKey="Siddell, Stuart G" sort="Siddell, Stuart G" uniqKey="Siddell S" first="Stuart G" last="Siddell">Stuart G. Siddell</name><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name></country><country name="Allemagne"><noRegion><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name></noRegion><name sortKey="Barchet, Winfried" sort="Barchet, Winfried" uniqKey="Barchet W" first="Winfried" last="Barchet">Winfried Barchet</name></country><country name="États-Unis"><region name="Missouri (État)"><name sortKey="Szretter, Kristy J" sort="Szretter, Kristy J" uniqKey="Szretter K" first="Kristy J" last="Szretter">Kristy J. Szretter</name></region><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C" last="Baker">Susan C. 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