Thompson Matthew G, Lynch Kristen W
Department of Biochemistry and Biophysics Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cold Spring Harb Symp Quant Biol. 2019;84:123-131. doi: 10.1101/sqb.2019.84.039040.
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.
可变剪接是哺乳动物细胞和病毒都采用的一种普遍存在的基因调控机制，用于扩展其基因组编码能力。剪接过程以及指导该过程的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，因此必须夺取宿主剪接体和许多相关调控蛋白，以便正确处理其基因。在这里，我们以甲型流感病毒为例，既描述病毒如何利用宿主剪接因子来调控自身剪接，也提供病毒感染如何反过来改变宿主剪接的例子。重要的是，我们表明宿主剪接中至少一些由病毒诱导的变化发生在改变流感病毒复制效率的基因中。我们强调，加强对宿主和病毒剪接之间机制相互作用及其功能后果的理解，对于发现潜在的抗病毒弱点至关重要。
