Disruption of nonsense-mediated decay by the multifunctional long-distance movement protein of Pea enation mosaic virus 2

Nonsense-mediated decay (NMD) is an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, forcing viruses to counteract the NMD pathway for successful amplification in host cells. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, We report that the Pea enation mosaic virus 2 long-distance movement protein, p26, protects a subset of natural cellular NMD-target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, RNA-seq revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with nearly half of NMD-targets increasing in abundance. Widespread changes in host transcriptomes are common during RNA virus infections and these results suggest that virus-mediated NMD-inhibition may be a major contributing factor. Overall design: Identified differentially expressed transcripts in Nicotiana benthamiana in the presence of an NMD inhibitor, p26 over-expression, and PEMV2 infection

无义介导的RNA降解（Nonsense-mediated decay, NMD）是一类RNA调控通路，可降解带有长3'非翻译区（3' UTR）的天然信使RNA与异常信使RNA。NMD可靶向多种RNA病毒家族，迫使病毒必须拮抗NMD通路才能在宿主细胞中完成成功扩增。本研究以模式植物本氏烟草（Nicotiana benthamiana）为材料，通过转录组全景分析手段，发现豌豆耳突花叶病毒2号（PEMV2）的长距离移动蛋白p26能够保护一类天然细胞内的NMD靶向转录本，尤其是那些带有长片段、复杂二级结构且高GC含量的3'非翻译区的转录本。此外，RNA测序（RNA-seq）结果显示，PEMV2感染期间宿主的NMD通路存在严重功能异常，近半数NMD靶向转录本的丰度出现上调。RNA病毒感染宿主期间，其转录组发生广泛变化已是普遍现象，本研究结果提示病毒介导的NMD抑制或许是这一现象的主要促成因素之一。实验整体设计：检测在添加NMD抑制剂、过表达p26以及PEMV2感染三种条件下，本氏烟草中的差异表达转录本。