MicroRNA-mediated regulation of viral replication

MicroRNA介导的病毒复制调节

基本信息

批准号：
BB/F02360X/1
负责人：
Catherine Jopling
金额：
$ 105.57万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF02360X%2F1
关键词：
MicroRNA mediated regulation viral replication

项目摘要

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.

基因是DNA的长部分，这些部分被复制成类似物质RNA的长分子。这些信使RNA被称为核糖体的机器解释，以制造蛋白质，这些蛋白质在我们的细胞中执行功能。最近，发现某些基因被复制为简短的RNA序列，称为microRNA。 microRNA不用于制造蛋白质本身，而是与具有microRNA匹配序列的Messenger RNA分子结合。这种结合导致降低了该信使RNA的蛋白质量，因此对于控制细胞中存在的特定蛋白质水平以及细胞的行为很重要。丙型肝炎病毒（HCV）基因组由一条长的RNA组成，它进入肝细胞，在该肝细胞中用作制造HCV蛋白的模板。这些制作了更多的HCV RNA副本，该过程称为病毒复制。我最近发现，仅在肝脏中发现的microRNA miR-122与HCV RNA中的位点结合。需要这种结合才能发生病毒复制。这种对病毒复制的积极影响与对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结合位点移至不同基因中的另一个位置，则可以抑制蛋白质合成。这项研究的目的是了解microRNA如何介导两个不同的过程。由于绑定位点的位置对于其功能很重要，因此HCV版本将使用不同位置的站点制作，并经过测试以查看该站点的要求。已知蛋白质对microRNA的功能很重要，因此将检测到与miR-122相互作用的蛋白质与HCV RNA相互作用。这些将与microRNA用来抑制蛋白质合成的蛋白质进行比较。最后，将进行实验以检测HCV复制周期中的miR-122相互作用。这些实验共同解释了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生物学小组中进行。该小组的研究人员在RNA的几个不同方面工作，并以最先进的新实验室为基于RNA研究的所有必要设施。