Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection.
Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection.
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DOI：
10.1093/nar/gky029
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发表时间：
2018-06-20
影响因子：
14.9
通讯作者：
Pager CT
中科院分区：
文献类型：
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作者：
McIntyre W;Netzband R;Bonenfant G;Biegel JM;Miller C;Fuchs G;Henderson E;Arra M;Canki M;Fabris D;Pager CT
已知有超过140种转录后修饰（PTMs）修饰细胞RNA，但它们在病毒RNA中的发生率、身份和意义仍然很大程度上未知。我们已经开发了一种不可知的分析方法来全面调查病毒和细胞RNA上的PTM。具体而言，我们使用质谱分析从感染寨卡病毒、登革热病毒、丙型肝炎病毒（HCV）、脊髓灰质炎病毒和人类免疫缺陷病毒1型的细胞中分离的总RNA上的PTM。所有五种RNA病毒都显著改变了全球PTM景观。通过亲和捕获分离的单个病毒基因组的PTM谱的检查揭示了病毒RNA上的过多PTM，其远远超过了少数充分表征的修饰。直接比较病毒表位转录组鉴定了常见的和病毒特异性的PTM。特别是，特异性二甲基胞嘧啶修饰仅存在于来自病毒感染细胞的总RNA中，以及细胞内HCV RNA和来自寨卡病毒和HCV病毒体的病毒RNA中。此外，二甲基胞嘧啶丰度在病毒感染过程中调制的细胞死亡盒RNA解旋酶DDX6。通过打开病毒PTM的潘多拉盒子，本报告提出了许多关于PTM功能的问题和假设，并强烈支持PTM作为RNA病毒颠覆宿主和逃避细胞监视系统的新一层调控。
More than 140 post-transcriptional modifications (PTMs) are known to decorate cellular RNAs, but their incidence, identity and significance in viral RNA are still largely unknown. We have developed an agnostic analytical approach to comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used mass spectrometry to analyze PTMs on total RNA isolated from cells infected with Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human immunodeficiency virus type 1. All five RNA viruses significantly altered global PTM landscapes. Examination of PTM profiles of individual viral genomes isolated by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds the handful of well-characterized modifications. Direct comparison of viral epitranscriptomes identified common and virus-specific PTMs. In particular, specific dimethylcytosine modifications were only present in total RNA from virus-infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV virions. Moreover, dimethylcytosine abundance during viral infection was modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora’s box on viral PTMs, this report presents numerous questions and hypotheses on PTM function and strongly supports PTMs as a new tier of regulation by which RNA viruses subvert the host and evade cellular surveillance systems.
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影响因子：
6.4
作者：
Durbin AF;Wang C;Marcotrigiano J;Gehrke L
通讯作者：
Gehrke L
影响因子：
14.9
作者：
Ding, Y;Chan, CY;Lawrence, CE
通讯作者：
Lawrence, CE
影响因子：
2
作者：
Collings, BA;Campbell, JM;Douglas, DJ
通讯作者：
Douglas, DJ
影响因子：
14.9
作者：
Dunin-Horkawicz, Stanislaw;Czerwoniec, Anna;Gajda, Michal J.;Feder, Marcin;Grosjean, Henri;Bujnicki, Janusz M.
通讯作者：
Bujnicki, Janusz M.
病毒mRNA帽的2'-O甲基化通过IFIT家族成员逃避了宿主的限制。
影响因子：
64.8
作者：
通讯作者：
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