Functional and Mechanistic Interplay of Host and Viral Alternative Splicing Regulation during Influenza Infection.
Functional and Mechanistic Interplay of Host and Viral Alternative Splicing Regulation during Influenza Infection.
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DOI：
10.1101/sqb.2019.84.039040
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Matthew G. Thompson;K. Lynch
中科院分区：
文献类型：
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作者：
Matthew G. Thompson;K. Lynch
选择性剪接是一种普遍存在的基因调控机制，哺乳动物细胞和病毒都利用它来扩增其基因组编码能力。剪接的过程和指导这一过程的RNA序列在哺乳动物和病毒转录本中是相同的;然而，病毒缺乏剪接机制，因此必须篡夺宿主剪接体和许多相关的调节蛋白，以便正确地加工它们的基因。在这里，我们使用甲型流感病毒的例子来描述病毒如何利用宿主剪接因子来调节自身的剪接，并提供病毒感染如何反过来改变宿主剪接的例子。重要的是，我们表明，至少有一些病毒诱导的宿主剪接的变化发生在基因中，改变流感复制的效率。我们强调，在发现潜在的抗病毒脆弱性方面，增加对宿主和病毒剪接之间的相互作用机制及其功能后果的理解非常重要。
Alternative splicing is a pervasive gene regulatory mechanism utilized by both mammalian cells and viruses to expand their genomic coding capacity. The process of splicing and the RNA sequences that guide this process are the same in mammalian and viral transcripts; however, viruses lack the splicing machinery and therefore must usurp both the host spliceosome and many of the associated regulatory proteins in order to correctly process their genes. Here, we use the example of the influenza A virus to both describe how viruses utilize host splicing factors to regulate their own splicing and provide examples of how viral infection can, in turn, alter host splicing. Importantly, we show that at least some of the viral-induced changes in host splicing occur in genes that alter the efficiency of influenza replication. We emphasize the importance of increased understanding of the mechanistic interplay between host and viral splicing, and its functional consequences, in uncovering potential antiviral vulnerabilities.