The RNA Institute, University at Albany-SUNY, Albany, NY 12222, USA.
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Nucleic Acids Res. 2018 Jun 20;46(11):5776-5791. doi: 10.1093/nar/gky029.
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.
已知超过 140 种转录后修饰（PTM）修饰细胞 RNA，但病毒 RNA 中的 PTM 发生率、身份和意义在很大程度上仍然未知。我们开发了一种盲目分析方法，以全面调查病毒和细胞 RNA 上的 PTM。具体来说，我们使用质谱分析法分析了感染寨卡病毒、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 的细胞中分离的总 RNA 上的 PTM。这五种 RNA 病毒都显著改变了全局 PTM 景观。通过亲和捕获分离的单个病毒基因组的 PTM 分析表明，病毒 RNA 上存在大量 PTM，远远超过少数几种特征明确的修饰。病毒转录组修饰的直接比较确定了共同和病毒特异性的 PTM。特别是，特定的二甲基胞嘧啶修饰仅存在于病毒感染细胞的总 RNA 中，以及细胞内 HCV RNA 和寨卡病毒和 HCV 病毒粒子中的病毒 RNA 中。此外，在病毒感染过程中二甲基胞嘧啶的丰度受细胞 DEAD 盒 RNA 解旋酶 DDX6 的调节。本报告通过揭示病毒 PTM，提出了许多关于 PTM 功能的问题和假设，并强烈支持 PTM 作为一种新的调节层次，通过该调节层次，RNA 病毒颠覆宿主并逃避细胞监视系统。
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