elF4E - susceptibility factor for potyvirus infection with potential predictive resistance strategies

在这个项目中，我们想了解一种特殊的蛋白质，它可以帮助一些病毒感染植物。这种蛋白质被称为真核翻译起始因子4E，或elF4E，存在于高等生物的所有细胞中，并通过阅读信使RNA(MRNA)在产生其他蛋白质方面发挥核心作用。我们证明了没有这种蛋白的植物可以抵抗某些病毒的侵染。虽然依赖于这种蛋白质的特定病毒(马铃薯Y病毒)的RNA与mRNAs的结构略有不同，但我们认为elF4E在帮助病毒RNA产生其他蛋白质方面起着非常相似的作用。从对不同作物抗马铃薯Y病毒的研究中，我们了解到存在不同形式的elF4E，它们不能辅助马铃薯Y病毒的侵染。看来，这些抗性植物无法产生病毒蛋白与elF4E未能与病毒RNA的起始端结合有关。在我们对豌豆抗豌豆马铃薯Y病毒(称为豌豆种子传花叶病毒：PSbMV)的研究中，我们还发现了elF4E另一个非常令人惊讶的特性。它也有能力帮助PSbMV从一个细胞转移到另一个细胞，通过植物传播感染。因此，改变的elF4E阻止病毒在抗性豌豆植株中复制和传播。大分子在细胞间的运动对植物的生长和发育也很重要，尽管所涉及的机制通常知之甚少。因此，对elF4E的研究可以告诉我们生物学的几个非常重要的领域：病毒如何感染植物和植物的抗性潜力，RNA的翻译以产生蛋白质，以及细胞间的通讯。我们将对elF4E蛋白进行新的改变，并将这些改变与植物进行mRNA翻译、病毒复制和病毒在细胞之间移动的潜力联系起来。我们还将确定elF4E和病毒蛋白在复合体中结合的原子结构。通过这种方式，我们将了解这些蛋白质是如何结合在一起的，以及我们需要做些什么来阻止它的发生。根据这些信息，我们将发现不能形成复合体的突变豌豆植株，因此具有对PSbMV和其他马铃薯Y病毒表现出新抗性的植物。我们还将确定实验植物拟南芥的突变体，这将为进一步剖析细胞间的通讯建立一系列遗传和生物学工具。

In this project we want to understand a special protein that helps some viruses to infect plants. This protein, called eukaryotic translation initiation factor 4E, or elF4E, exists in all cells of higher organisms and plays a central role in producing other proteins by reading messenger RNA (mRNA). We showed that plants without this protein can be resistant to infection with some viruses. Although specific viruses (Potyviruses) that depend upon this protein have an RNA with a slightly different structure from that of mRNAs, we believe that elF4E plays a very similar role in helping the viral RNA to produce other proteins. From studies of different crop plants that are resistant to potyviruses, we know of the existence of different forms of elF4E which cannot assist potyvirus infection. It appears that the inability of these resistant plants to produce viral proteins is associated with a failure of elF4E to bind to the starting-end of the viral RNA. In our studies of peas resistant to pea potyvirus (called Pea seed-borne mosaic virus: PSbMV), we have also identified another very surprising property of elF4E. It also has the ability to assist PSbMV to move from one cell to another, to spread the infection through the plant. Hence, altered elF4E prevents the virus from both replicating and spreading in resistant pea plants. Cell-to-cell movement of large molecules is also important for plant growth and development although the mechanisms involved are generally very poorly understood. Therefore, the study of elF4E can tell us about several very important areas of biology: how viruses infect plants and the potential for resistance in plants, the translation of RNAs to produce proteins, and cell-to-cell communication. We will make new changes in the elF4E protein and relate these to the potential of plants to carry out mRNA translation, virus replication, and virus movement from cell to cell. We will also determine the atomic structure of the elF4E and virus proteins that join together in a complex. In this way we will understand how the proteins join together and what we need to do to stop it happening. From this information we will identify mutant pea plants where the complex cannot form and therefore plants with potential to exhibit new resistance to PSbMV and other potyviruses. We will also identify mutants for the experimental plant Arabidopsis, which will establish a range of genetic and biological tools for further dissection of cell-to-cell communications.