Exoribonuclease-Resistant RNAs Exist within both Coding and Noncoding Subgenomic RNAs
Exoribonuclease-Resistant RNAs Exist within both Coding and Noncoding Subgenomic RNAs
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DOI：
10.1128/mbio.02461-18
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发表时间：
2018-11-01
期刊：
影响因子：
6.4
通讯作者：
Kieft, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Steckelberg, Anna-Lena;Vicens, Quentin;Kieft, Jeffrey S.
许多病毒产生对感染至关重要的蛋白质编码和非编码亚基因组RNA（sgRNA）。最近发现的用于病毒sgRNA产生的途径使用外切核糖核酸酶抗性RNA（xrRNA），其是阻断RNA的进行性外切核糖核酸降解的离散折叠RNA元件。xrRNA广泛存在于感染动物的黄病毒中，但仅在植物病毒属石竹病毒的三个成员中发现。此外，xrRNA仅在病毒RNA的3'非翻译区（3'UTR）中发现，在那里它们产生非编码sgRNA。在其他病毒中存在的xrRNA元件的程度，其环状折叠的保守性，以及xrRNA在不同环境中操作的能力都是未知的。使用计算工具和生物化学测定，我们发现xrRNA元件遍布两个大家族的植物感染RNA病毒，证明了它们的重要性和广泛的用途。序列和功能要求的比较表明，所有采用的特征环状折叠。出乎意料的是，这些新发现的xrRNA中的许多位于基因间区域而不是3“UTR中，并且一些与编码病毒蛋白的亚基因组RNA的5'末端相关。这表明xrRNA参与编码和非编码亚基因组RNA的产生，并且可以作为调节RNA水平和蛋白质表达的更广泛机制的一部分。这些发现扩展了xrRNA的潜在作用，并表明xrRNA可能代表了一个更普遍的策略，RNA成熟和维护比以前所知的。重要性在感染过程中，病毒经常产生亚基因组RNA（sgRNA），要么作为蛋白质合成的模板或作为“核糖核酸调节子”，相互作用，并影响病毒和细胞的机器。最近，发现了一种产生sgRNA的机制，该机制取决于特定结构的RNA元件（xrRNA）的存在。然而，这种机制的使用程度，元件的发现位置，它们的结构多样性以及这种途径产生的sgRNA类型尚不清楚。本文描述了在两大植物病毒家族中发现的这些结构化RNA元件，并表明它们用于产生蛋白质编码的sgRNA和“核糖核酸调节”RNA。这些发现提供的证据表明，基于xrRNA的RNA成熟途径可能比以前预期的更广泛，并且它们参与产生各种不同功能的RNA。
Many viruses produce protein-coding and noncoding subgenomic RNAs (sgRNAs) that are critical for infection. A recently discovered pathway for viral sgRNA production uses exoribonuclease-resistant RNAs (xrRNAs), discrete folded RNA elements that block the processive exoribonucleolytic degradation of RNA. xrRNAs are widespread in animal-infecting flaviviruses but had been found only in three members of the plant virus genus Dianthovirus. Also, xrRNAs had been found only in the 3' untranslated regions (3'UTRs) of viral RNAs, where they produce noncoding sgRNAs. The degree to which xrRNA elements exist in other viruses, the conservation of their ring-like fold, and the ability of xrRNAs to operate in diverse contexts were unknown. Using computational tools and biochemical assays, we discovered xrRNA elements pervading two large families of plant-infecting RNA viruses, demonstrating their importance and widespread utility. Comparison of the sequences and functional requirements suggests that all adopt the characteristic ring-like fold. Unexpectedly, many of these newly discovered xrRNAs are located in intergenic regions rather than 3"UTRs, and some are associated with the 5' ends of subgenomic RNAs that encode viral proteins. This suggests that xrRNAs are involved in the production of both coding and noncoding subgenomic RNAs and can operate as part of broader mechanisms to regulate RNA levels and protein expression. These discoveries expand the potential roles for xrRNAs and suggest that xrRNAs may represent a more general strategy for RNA maturation and maintenance than previously known.IMPORTANCE During infection, viruses often produce subgenomic RNAs (sgRNAs) that either serve as the template for protein synthesis or act as "riboregulators" that interact with and influence the viral and cellular machinery. Recently, a mechanism for producing sgRNAs was found that depends on the presence of specifically structured RNA elements (xrRNAs). However, the degree to which this mechanism is used, where the elements are found, their structural diversity, and what types of sgRNAs are produced by this pathway were unclear. This article describes the discovery of these structured RNA elements in two large families of plant viruses and shows that they are used to produce both protein-coding sgRNAs and "riboregulatory" RNAs. These discoveries provide evidence that xrRNA-based RNA maturation pathways may be more widespread than previously anticipated and that they are involved in producing a variety of RNAs of diverse functions.