The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay
The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay
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DOI：
10.1128/mbio.00204-20
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发表时间：
2020-03-01
期刊：
影响因子：
6.4
通讯作者：
Simon, Anne E.
中科院分区：
文献类型：
--
作者：
May, Jared P.;Johnson, Philip Z.;Simon, Anne E.
无义介导的衰变(NMD)途径对RNA病毒提出了挑战，其终止密码子位于扩展的3‘非翻译区(UTRs)之前。豌豆冠状花叶病毒2(PEMV2)是一种非节段性正性RNA病毒，其3‘端非编码区异常长，对NMD易感。为了确定系统性感染，PEMV2长距离移动蛋白P26先前被证明既可以稳定病毒RNA，又可以结合它们通过植物的血管系统进行运输。目前的研究表明，P26既能保护病毒信使RNA免受NMD的侵袭，也能保护非病毒信使RNA免受NMD的伤害。虽然P26定位于细胞质和核仁，但P26仅在细胞质发挥其抗NMD的作用，而不依赖于远距离运动。在模式植物烟草中使用转录组范围的方法，P26保护了细胞NMD靶转录子的子集，特别是那些包含长的、结构化的、富含GC的3‘UTRs的转录子。此外，转录组测序(RNA-seq)显示，在PEMV2感染过程中，NMD途径高度失调，1,820个(48%)NMD靶点大量增加。寄主转录组的广泛变化在植物RNA病毒侵染过程中是常见的，这些结果表明，至少在某些情况下，病毒介导的NMD抑制可能是一个主要的促成因素。重要的无义介导的衰变(NMD)是一种RNA调控途径，它降解具有长3‘非翻译区的天然和有缺陷的信使RNA。NMD针对不同的RNA病毒家族，需要病毒中和NMD途径才能在宿主细胞中成功扩增。豌豆繁殖花叶病毒2(PEMV2)长距离移动所需的一种蛋白质也被证明可以保护病毒和宿主mRNAs免受NMD的侵袭。对烟草转录组的RNA-SEQ分析表明，PEMV2感染显著损害了寄主NMD途径。RNA病毒通常会引起宿主基因表达的大规模变化，并且像PEMV2一样，可能会使用NMD抑制来改变宿主转录组，以努力增加病毒的扩增。
The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant's vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.