For over a decade, studies of messenger RNA regulation have revealed an unprecedented level of connectivity between the RNA pool and global gene expression. These connections are underpinned by a vast array of RNA elements that coordinate RNA-protein and RNA-RNA interactions, each directing mRNA fate from transcription to translation. Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as “Host Shutoff”. This takeover of the host cell is mechanistically orchestrated by a number of non-homologous virally encoded endoribonucleases. Recent large-scale screens estimate that over 70 % of the host transcriptome is decimated by the expression of these viral nucleases. While this takeover strategy seems extraordinarily well conserved, each viral endonuclease has evolved to target distinct mRNA elements. Herein, we will explore each of these RNA structures/sequence features that render messenger RNA susceptible or resistant to viral endonuclease cleavage. By further understanding these targeting and escape mechanisms we will continue to unravel untold depths of cellular RNA regulation that further underscores the integral relationship between RNA fate and the fate of the cell.

十多年来，对信使 RNA 调控的研究揭示了 RNA 库和全球基因表达之间前所未有的连接水平。这些联系由大量协调 RNA-蛋白质和 RNA-RNA 相互作用的 RNA 元素支撑，每一个都指导 mRNA 从转录到翻译的命运。因此，病毒已经进化出一系列策略来靶向这些 RNA 特征并最终控制它们影响的途径，这些策略有助于全球关闭宿主基因表达机制，称为“宿主关闭”。这种对宿主细胞的接管是由许多非同源病毒编码的核糖核酸内切酶机械地协调的。最近的大规模筛选估计超过 70% 的宿主转录组被这些病毒核酸酶的表达所破坏。虽然这种接管策略似乎非常保守，但每种病毒核酸内切酶都已进化为靶向不同的 mRNA 元件。在这里，我们将探索这些 RNA 结构/序列特征中的每一个，这些特征使信使 RNA 对病毒核酸内切酶切割敏感或有抗性。通过进一步了解这些靶向和逃逸机制，我们将继续揭示细胞 RNA 调控的无限深度，这进一步强调了 RNA 命运与细胞命运之间的整体关系。我们将探索这些 RNA 结构/序列特征中的每一个，这些特征使信使 RNA 对病毒核酸内切酶切割敏感或具有抗性。通过进一步了解这些靶向和逃逸机制，我们将继续揭示细胞 RNA 调控的无限深度，这进一步强调了 RNA 命运与细胞命运之间的整体关系。我们将探索这些 RNA 结构/序列特征中的每一个，这些特征使信使 RNA 对病毒核酸内切酶切割敏感或具有抗性。通过进一步了解这些靶向和逃逸机制，我们将继续揭示细胞 RNA 调控的无限深度，这进一步强调了 RNA 命运与细胞命运之间的整体关系。