ABSTRACT

Beyond their high clinical relevance worldwide, flaviviruses (comprising dengue and Zika viruses) are of particular interest to understand the spatiotemporal control of RNA metabolism. Indeed, their positive single-stranded viral RNA genome (vRNA) undergoes in the cytoplasm replication, translation and encapsidation, three steps of the flavivirus life cycle that are coordinated through a fine-tuned equilibrium. Over the last years, RNA methylation has emerged as a powerful mechanism to regulate messenger RNA metabolism at the posttranscriptional level. Not surprisingly, flaviviruses exploit RNA epigenetic strategies to control crucial steps of their replication cycle as well as to evade sensing by the innate immune system. This review summarizes the current knowledge about vRNA methylation events and their impacts on flavivirus replication and pathogenesis. We also address the important challenges that the field of epitranscriptomics faces in reliably and accurately identifying RNA methylation sites, which should be considered in future studies on viral RNA modifications.

摘要

除了在全球范围内具有很高的临床相关性外，黄病毒（包括登革热和寨卡病毒）对于了解 RNA 代谢的时空控制特别感兴趣。事实上，它们的阳性单链病毒 RNA 基因组 (vRNA) 在细胞质复制、翻译和衣壳化过程中经历了黄病毒生命周期的三个步骤，这些步骤通过微调平衡进行协调。在过去几年中，RNA 甲基化已成为一种在转录后水平调节信使 RNA 代谢的强大机制。毫不奇怪，黄病毒利用 RNA 表观遗传策略来控制其复制周期的关键步骤以及逃避先天免疫系统的感知。本综述总结了当前关于 vRNA 甲基化事件及其对黄病毒复制和发病机制的影响的知识。我们还解决了表观转录组学领域在可靠和准确地识别 RNA 甲基化位点方面面临的重要挑战，这在未来的病毒 RNA 修饰研究中应予以考虑。