RNA-mediated Regulation of RNA Virus Replication

含有RNA基因组的病毒对动植物的健康构成严重威胁。我们的研究项目调查了这种感染性病原体繁殖周期中的基本步骤。我们的实验室专注于基于RNA的调控领域-病毒RNA基因组中的调控RNA元件控制感染过程中的关键步骤的机制。我们研究植物病毒科的成员，这是一种小的球形病毒，包含单链、正感(即信使感官)RNA基因组。这一组中的许多病毒会在各种重要的农作物上引起疾病。我们的研究集中在该病毒家族的两个成员，番茄丛矮病毒(TBSV)和红三叶坏死花叶病毒(RCNMV)，这两种病毒是从分子水平上理解侵染过程的优秀模式病毒。我们研究计划的长期目标是了解这些RNA病毒如何利用局部和全球RNA结构来控制其繁殖周期中的各个步骤。在这一授权期内，我们的短期目标包括：(1)研究无帽病毒RNA基因组的5‘末端如何抵抗核酸酶攻击(2)了解病毒RNA基因组如何折叠成控制其基因表达的构象(3)识别与病毒RNA元件结合并促进病毒基因组复制的细胞蛋白质(4)确定由两个RNA片段组成的病毒RNA基因组的全球架构为解决这些问题，我们将使用不同的方法，包括计算、生化、结构、分子和细胞技术。这些研究的结果将使我们更好地理解这些病毒是如何利用它们的RNA基因组来控制感染过程的。理解基于RNA的调控很重要，原因有几个。首先，它代表了许多RNA病毒使用的一种基本和独特的调节策略，因此我们的结果可能与其他RNA病毒相关，甚至可能与细胞mRNAs相关。其次，我们在这一领域的工作有助于促进这一新概念的提出，即除了局部RNA元件外，病毒RNA基因组的整体结构对控制病毒过程也很重要。第三，基于RNA的病毒调控知识在生物技术中具有潜在的有益应用；例如，通过开发针对和抑制病毒RNA元件活性的新的抗病毒策略，或通过改变其在病毒基蛋白表达载体中的活性，从而提高其效率。

Viruses that contain RNA genomes represent a serious threat to the health of plants and animals. Our research program investigates fundamental steps in the reproductive cycle of this type of infectious agent. Our laboratory focuses on the area of RNA-based regulation - the mechanisms by which regulatory RNA elements within viral RNA genomes control critical steps in the infectious process. We study members of the plant virus family Tombusviridae, which are small spherical viruses that contain single-stranded, plus-sensed (i.e. messenger-sensed) RNA genomes. Many viruses in this group cause diseases in a variety of important crop plants. Our research focuses on two members of this virus family, Tomato bushy stunt virus (TBSV) and Red clover necrotic mosaic virus (RCNMV), which are excellent model viruses for understanding the infectious process at the molecular level. The long-term objective of our research program is to understand how these RNA viruses utilize local and global RNA structures to control various steps in their reproductive cycles. In this granting period our short-term goals include: (1) Investigating how the 5'-terminus of an uncapped viral RNA genome resists nuclease attack (2) Understanding how viral RNA genomes fold into conformations that control their gene expression (3) Identifying cellular proteins that bind to viral RNA elements and promote viral genome replication (4) Determining the global architecture of a viral RNA genome that consists of two RNA segments To address these questions, we will use different methods, including computational, biochemical, structural, molecular, and cellular techniques. The results derived from these studies will allow us to better comprehend how these viruses use their RNA genomes to control the infectious process. Understanding RNA-based regulation is important for several reasons. First, it represents a fundamental and distinctive type of regulatory strategy used by many RNA viruses, so our results will likely be relevant to other RNA viruses, and possibly even cellular mRNAs. Second, our work in this field has helped to promote the novel concept that, in addition to local RNA elements, the overall architecture of viral RNA genomes is also important for controlling viral processes. Third, knowledge of RNA-based virus regulation has potential beneficial applications in biotechnology; e.g. through the development of novel antiviral strategies that target and inhibit the activity of viral RNA elements or by modifying their activities in, for example, virus-based protein expression vectors, so as to improve their efficiencies.