m6A modification controls the innate immune response to infection by targeting type I interferons
| Autor: | Ella Gillis, Noam Stern-Ginossar, Mirko Trilling, Jacob H. Hanna, Modi Safra, Clara Soyris, Schraga Schwartz, Aharon Nachshon, Nehemya Friedman, Shay Geula, Roni Winkler, Lior Lasman, Michal Mandelboim, Vu Thuy Khanh Le-Trilling, Julie Tai-Schmiedel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Messenger RNA Innate immune system medicine.medical_treatment MRNA modification Immunology RNA Biology Virus 3. Good health Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cytokine Interferon medicine Immunology and Allergy Gene 030215 immunology medicine.drug |
| Zdroj: | Nature Immunology |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-018-0275-z |
| Popis: | N6-methyladenosine (m6A) is the most common mRNA modification. Recent studies have revealed that depletion of m6A machinery leads to alterations in the propagation of diverse viruses. These effects were proposed to be mediated through dysregulated methylation of viral RNA. Here we show that following viral infection or stimulation of cells with an inactivated virus, deletion of the m6A 'writer' METTL3 or 'reader' YTHDF2 led to an increase in the induction of interferon-stimulated genes. Consequently, propagation of different viruses was suppressed in an interferon-signaling-dependent manner. Significantly, the mRNA of IFNB, the gene encoding the main cytokine that drives the type I interferon response, was m6A modified and was stabilized following repression of METTL3 or YTHDF2. Furthermore, we show that m6A-mediated regulation of interferon genes was conserved in mice. Together, our findings uncover the role m6A serves as a negative regulator of interferon response by dictating the fast turnover of interferon mRNAs and consequently facilitating viral propagation. |
| Databáze: | OpenAIRE |
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