Influenza virus mRNA trafficking through host nuclear speckles.
Influenza virus mRNA trafficking through host nuclear speckles.
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DOI：
10.1038/nmicrobiol.2016.69
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发表时间：
2016-05-27
影响因子：
28.3
通讯作者：
Fontoura BM
中科院分区：
文献类型：
--
作者：
Mor A;White A;Zhang K;Thompson M;Esparza M;Muñoz-Moreno R;Koide K;Lynch KW;García-Sastre A;Fontoura BM
甲型流感病毒是一种人类病原体，其基因组由在细胞核中复制的八个病毒RNA片段组成。两种病毒mRNA是选择性剪接的。未剪接的M1 mRNA被翻译成基质M1蛋白，而离子通道M2蛋白在选择性剪接后产生。这些蛋白质是病毒运输和出芽的关键介质。我们发现，流感病毒利用核斑点，以促进转录后剪接的M1 mRNA。我们将病毒NS1蛋白和细胞因子先前未知的作用分配给核内运输途径，该途径将病毒M1 mRNA靶向核斑点，介导这些核小体的剪接，并将剪接的M2 mRNA从核中输出。由于核斑点是剪接因子的储存位点，剪接因子使这些位点在转录基因时剪接细胞前体mRNA，因此我们揭示了核斑点的功能颠覆以促进病毒基因表达。
Influenza A virus is a human pathogen whose genome is comprised of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein while the ion channel M2 protein is generated after alternative splicing. These proteins are critical mediators of viral trafficking and budding. We show that influenza virus utilizes nuclear speckles to promote post-transcriptional splicing of its M1 mRNA. We assign previously unknown roles for the viral NS1 protein and cellular factors to an intranuclear trafficking pathway that targets the viral M1 mRNA to nuclear speckles, mediates splicing at these nuclear bodies, and exports the spliced M2 mRNA from the nucleus. Since nuclear speckles are storage sites for splicing factors, which leave these sites to splice cellular pre-mRNAs at transcribing genes, we reveal a functional subversion of nuclear speckles to promote viral gene expression.