Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus

Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus
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DOI:
10.1038/ncomms4259
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发表时间:
2014-02
影响因子:
16.6
通讯作者:
Deng, Tao
Deng, Tao
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cui, Sheng;Jin, Qi;Wang, Jianwei;Deng, Tao

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甲型流感病毒的核糖核蛋白(RNP)负责病毒RNA在细胞核内的转录和复制。这些过程需要宿主因子和RNP组件之间的相互作用。在这里,我们报告了脆性X智力低下蛋白(FMRP)靶向流感病毒RNA合成机制,并促进病毒在细胞培养和小鼠体内的复制。我们证明了FMRP与病毒RNP短暂结合,并通过RNA介导的与核蛋白的相互作用刺激病毒RNP组装。此外,FMRP的HH2结构域介导其与核蛋白的联系。从一例脆性X综合征患者中发现的KH2结构域的一个点突变(I304N)破坏了FMRP与核蛋白的结合,并取消了FMRP参与病毒RNP组装的能力。我们得出结论,FMRP是流感病毒用来促进病毒RNP组装的关键宿主因子。我们的观察揭示了流感病毒RNA合成的机制,并为FMRP的功能提供了见解。
The ribonucleoprotein (RNP) of the influenza A virus is responsible for the transcription and replication of viral RNA in the nucleus. These processes require interplay between host factors and RNP components. Here, we report that the Fragile X mental retardation protein (FMRP) targets influenza virus RNA synthesis machinery and facilitates virus replication both in cell culture and in mice. We demonstrate that FMRP transiently associates with viral RNP and stimulates viral RNP assembly through RNA-mediated interaction with the nucleoprotein. Furthermore, the KH2 domain of FMRP mediates its association with the nucleoprotein. A point mutation (I304N) in the KH2 domain, identified from a Fragile X syndrome patient, disrupts the FMRP–nucleoprotein association and abolishes the ability of FMRP to participate in viral RNP assembly. We conclude that FMRP is a critical host factor used by influenza viruses to facilitate viral RNP assembly. Our observation reveals a mechanism of influenza virus RNA synthesis and provides insights into FMRP functions.
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