Function of EBV-encoded and EBV-induced mirRNA in latency and transformation

Coordinator:		Dr. Friedrich A. Grässer
Institution:		Institute für Infektionsmedizin, Institut für Virologie
Homepage:		wwwalt.med-rz.uniklinik-saarland.de/virologie

The Epstein-Barr Virus (EBV) induces infectious mononucleosis („kissing disease“) and is implicated in the induction of various tumours including Burkitt’s and Hodgkin’s lymphoma, post transplant lymphoma and also nasopharyngeal and gastric carcinoma. The virus contains the genetic information for 23 so-called microRNAs (miRNAs), the function of which for the virus is largely unknown. In addition to its own (viral) miRNAs, infection by EBV induces or represses the generation of cellular miRNAs. MiRNAs bind to messenger RNAs (mRNAs) and block the production of proteins derived from these mRNAs. The project aims at the identification of the cellular targets (mRNAs) for the viral and virus-regulated miRNAs. For this purpose, miRNA-containing complexes will be isolated and the targets (mRNAs) will be identified using molecular biological methods. For the isolation of these compelxes, we'll employ antibodies against so-called "Argonaute" ("Ago") proteins. The miRNA signatures of non-infected and virus-infected cells will be established and compared to the miRNA-bound mRNAs. The target structures will be predicted by mathematical algorithms. The predicted targets will be confirmed by biochemical and cell biological methods. The results will add to our understanding of (viral) tumorigenesis. The identification of proteins regulated by the viral or virus-induced miRNAs will lead to novel therapeutic targets in tumour therapy. A long-term goal is the Inhibition of tumour cell growth through blockage of virus- or virus-regulated miRNAs.



                             

Abbildung: Mechanismus der microRNA-vermittelten Hemmung der Proteinsynthese. Nach Bindung einer microRNA (miRNA) an ein „Argonaute“ („Ago“) Protein bindet dieses wiederum an die Zielstruktur der miRNA, eine Boten RNA („messengerRNA“,“ mRNA“). Nach Bildung des Komplexes aus Ago-Protein, miRNA und mRNA kommt es entweder direkt zur Hemmung der Proteinsynthese („Repression der Translation“) oder durch den Ago-vermittelten Abbau der mRNA zur Hemmung der Proteinsynthese.