The interaction of HCV with miR-122: mechanism and function

• Applicant: Dr. Sylvia Peter
• Subject Area: Virology
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 32153169

MicroRNAs are short cellular RNA molecules that regulate processes in development, tissue specificity and innate immunity. They are incorporated into a proteinacious complex (called RISC) and target partially complementary sequences in 3¿ untranslated regions (UTR) of mRNAs to mediate their translational repression. Recently, the liver-specific microRNA miR-122 was found to interact with the 5¿ UTR of the Hepatitis C virus (HCV) RNA genome and to be indispensable for the efficient replication of the virus. This is unexpected in respect to the fact that this cellular microRNA interacts with a viral genome and also has a positive impact on the replication of the virus, which contradicts the so far postulated repressional influence of microRNAs on translation. How miR-122 promotes viral replication is not yet understood. This finding also opens a new aspect in the lifecycle of HCV that needs to be investigated in further detail to determine new starting points for the development of antiviral therapies. In the proposed project I want to determine the function and mechanism of the miR-122-HCV interaction. With methods of cell biology and biochemistry I want to identify components of the miR-122-containing RISC-complex that interacts with the HCV genome and want to define the differences to a miR-122-containing RISC-complex in non-infected cells. Also, I propose to localize the crucial components of this interaction by fluorescence microscopy and compare it to non-infected cells. With the proposed set of experiments, I will be able to draw conclusions about the nature of this interaction and how it is different from the established negative regulatory functions of microRNAs.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Dr. Peter Sarnow