Nuclear TRIM25 Specifically Targets Influenza Virus Ribonucleoproteins to Block the Onset of RNA Chain Elongation.
Nuclear TRIM25 Specifically Targets Influenza Virus Ribonucleoproteins to Block the Onset of RNA Chain Elongation.
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Nuclear TRIM25 专门针对流感病毒核糖核蛋白来阻止 RNA 链伸长。
DOI：
10.1016/j.chom.2017.10.003
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发表时间：
2017-11-08
影响因子：
30.3
通讯作者：
Sawyer SL
中科院分区：
文献类型：
--
作者：
Meyerson NR;Zhou L;Guo YR;Zhao C;Tao YJ;Krug RM;Sawyer SL
TRIM25是一种E3泛素连接酶，可激活RIG-I促进抗病毒干扰素反应。来自所有甲型流感病毒株的NS1蛋白结合TRIM25，尽管不是所有病毒株都阻断干扰素应答，这提示TRIM25作用的其他机制。在这里，我们提出了TRIM25在特异性限制甲型流感病毒复制中的核作用。TRIM25通过直接机制抑制病毒RNA合成，不依赖于其泛素连接酶活性和干扰素途径。这种活性可被病毒NS1蛋白抑制。TRIM25对病毒RNA合成的抑制作用源于其与病毒核糖核蛋白（vRNPs）、含有单个病毒RNA片段的结构、病毒聚合酶和多个病毒核蛋白的结合。TRIM25的结合不会抑制病毒聚合酶合成带帽rna的病毒mRNA。相反，由于TRIM25阻止RNA进入聚合酶复合体，RNA链延伸的开始受到抑制。Meyerson等人在细胞核中鉴定出TRIM25的抗流感活性。TRIM25通过结合病毒含rna核糖核蛋白（vRNPs）特异性靶向流感病毒复制。TRIM25在感染细胞的细胞核中结合vRNPs，作为一种分子钳，剥夺病毒聚合酶的RNA模板。
TRIM25 is an E3 ubiquitin ligase that activates RIG-I to promote the anti-viral interferon response. The NS1 protein from all strains of influenza A virus bind TRIM25, although not all virus strains block the interferon response, suggesting alternative mechanisms for TRIM25 action. Here we present a nuclear role for TRIM25 in specifically restricting influenza A virus replication. TRIM25 inhibits viral RNA synthesis through a direct mechanism, independent of its ubiquitin ligase activity and the interferon pathway. This activity can be inhibited by the viral NS1 protein. TRIM25 inhibition of viral RNA synthesis results from its binding to viral ribonucleoproteins (vRNPs), the structures containing individual viral RNA segments, the viral polymerase, and multiple viral nucleoproteins. TRIM25 binding does not inhibit initiation of capped RNA-primed viral mRNA synthesis by the viral polymerase. Rather, the onset of RNA chain elongation is inhibited because TRIM25 prohibits the movement of RNA into the polymerase complex. Graphical Abstract Meyerson et al. identify an anti-influenza activity for TRIM25 in the nucleus. TRIM25 specifically targets influenza virus replication by binding viral RNA-containing ribonucleoproteins (vRNPs). TRIM25 binds vRNPs in nuclei of infected cells, acting as a molecular clamp that deprives the viral polymerase of its RNA template.
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影响因子：
16
作者：
Inn KS;Gack MU;Tokunaga F;Shi M;Wong LY;Iwai K;Jung JU
通讯作者：
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影响因子：
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Bieniasz PD
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通讯作者：
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