Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5.
Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5.
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作者：
宿主和病毒mRNA的2′-O-甲基化的生物学作用仍然难以捉摸。Thiel及其同事表明，这种修饰调节I型干扰素的诱导和对干扰素的敏感性。本文的在线版本（doi：10.1038/ni.1979）包含补充材料，可供授权用户使用。高等真核生物mRNA的5′帽结构存在核糖2′-O-甲基化。同样地，许多在真核生物细胞质中复制的病毒已经进化出2′-O-甲基转移酶来自主修饰它们的mRNA。然而，mRNA的2′-O-甲基化的生物学作用仍然是难以捉摸的。在这里，我们表明，2′-O-甲基化的病毒mRNA是关键参与颠覆诱导的I型干扰素。我们证明，人和小鼠冠状病毒突变体缺乏2′-O-甲基转移酶活性诱导I型干扰素的表达较高，并对I型干扰素高度敏感。值得注意的是，2′-O-甲基转移酶缺陷型病毒对I型干扰素的诱导依赖于细胞质RNA传感器Mda 5。Mda 5介导的病毒RNA传感和mRNA的2′-O-甲基化之间的这种联系表明，RNA修饰（如2′-O-甲基化）为区分自身和非自身mRNA提供了分子标记。本文的在线版本（doi：10.1038/ni.1979）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users. 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 online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users.
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影响因子：
6.7
作者：
Morin B;Coutard B;Lelke M;Ferron F;Kerber R;Jamal S;Frangeul A;Baronti C;Charrel R;de Lamballerie X;Vonrhein C;Lescar J;Bricogne G;Günther S;Canard B
通讯作者：
Canard B
影响因子：
5.4
作者：
Gosert, R;Kanjanahaluethai, A;Baker, SC
通讯作者：
Baker, SC
影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
影响因子：
64.8
作者：
NOMOTO, A;DETJEN, B;WIMMER, E
通讯作者：
WIMMER, E
病毒mRNA帽的2'-O甲基化通过IFIT家族成员逃避了宿主的限制。
影响因子：
64.8
作者：
通讯作者：
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