MicroRNA-mediated regulation of viral replication

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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.