MicroRNA-mediated regulation of viral replication

基因是DNA的长片段，被复制成类似物质RNA的长分子。这些信使rna被称为核糖体的机器解释成蛋白质，这些蛋白质在我们的细胞中执行功能。最近，人们发现一些基因被复制成非常短的RNA序列，被称为微RNA。microRNA本身并不用于制造蛋白质，而是与信使RNA分子结合，信使RNA分子与microRNA的序列相匹配。这种结合导致信使RNA产生的蛋白质数量减少，因此在控制细胞中存在的特定蛋白质的水平，从而控制细胞的行为方面很重要。丙型肝炎病毒（HCV）基因组由一长链RNA组成，它进入肝细胞，在那里被用作制造HCV蛋白质的模板。这些病毒会复制更多的HCV RNA，这一过程被称为病毒复制。我最近发现，仅在肝脏中发现的microRNA miR-122与HCV RNA中的一个位点结合。这种结合是病毒复制发生所必需的。这种对病毒复制的积极影响与mirna通常促进的蛋白质合成的负面影响非常不同。有趣的是，如果来自HCV的miR-122结合位点被移动到不同基因中的不同位置，它会抑制蛋白质合成。这项研究的目的是了解一个microRNA如何介导两种不同的过程。由于结合位点的位置对其功能很重要，因此将在不同位置制作不同版本的HCV，并对其进行测试，以了解对位点的要求是什么。已知蛋白质对microrna的功能很重要，因此将检测到在miR-122与HCV RNA相互作用时结合miR-122的蛋白质。这些将与microrna用来抑制蛋白质合成的蛋白质进行比较。最后，将进行实验来检测在HCV复制周期中miR-122何时相互作用。总之，这些实验将有助于解释miR-122如何能够调节HCV复制。这项研究将在诺丁汉大学新生物分子科学中心的RNA生物学小组进行。该小组的研究人员研究RNA的几个不同方面，并在最先进的新实验室工作，拥有RNA研究所需的所有设施。

Genes are long sections of DNA that are copied into long molecules of a similar substance, RNA. These messenger RNAs are interpreted by machines known as ribosomes to make proteins, which carry out the functions in our cells. Recently, it was found that some genes are copied to make very short sequences of RNA, known as microRNAs. MicroRNAs are not used to make protein themselves, but instead bind to messenger RNA molecules that have a matching sequence for the microRNA. This binding leads to a reduction in the amount of protein made from that messenger RNA, and so is important in controlling the levels of particular proteins present in a cell, and therefore the behaviour of the cell. The hepatitis C virus (HCV) genome is composed of a long strand of RNA, which enters liver cells where it is used as a template to make HCV proteins. These make more copies of the HCV RNA, a process known as viral replication. I recently found that miR-122, a microRNA that is only found in the liver, binds to a site in HCV RNA. This binding is needed for viral replication to occur. This positive effect on viral replication is very different to the negative effects on protein synthesis that miRNAs normally promote. Interestingly, if the miR-122 binding site from HCV is moved to a different place in a different gene, it acts to repress protein synthesis. The aim of this research is to understand how a microRNA can mediate two such different processes. As the location of the binding site is important for its function, versions of HCV will be made with sites in different locations and tested to see what the requirements for the site are. Proteins are known to be important for microRNAs to function, so proteins that bind to miR-122 while it interacts with HCV RNA will be detected. These will be compared to the proteins used by microRNAs to repress protein synthesis. Finally, experiments will be carried out to detect when in the HCV replication cycle miR-122 interacts. Together, these experiments will help to explain how miR-122 is able to regulate HCV replication. This research will be carried out in the RNA biology group in the new Centre for Biomolecular Sciences at the University of Nottingham. Researchers in the group work on several different aspects of RNA, and are based in state-of-the-art new laboratories with all the necessary facilities for RNA research.