Gene silencing by RNAi and DNA Methylation

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Posttranscriptionel Genesilencing (PTGS) is an epigenetic phenomenon which is elicited by double stranded RNA (RNAi) or the expression of antisense-RNA. Though parts of the molecular machinery are known, the mechanisms of this regulation are largely unsolved. Transkriptionel genesilencing (TGS) is found e.g. in mammalian imprinting and in cosuppression in. In both cases, differential de-novo methylation of DNA is observed. In plants, small double stranded (ds)RNAs appear to specify the DNA target to be methylated. A correlation between TGS and PTGS in Plants is suggested and currently intensely discussed. In mammals, antisense transcripts are found at several if not all imprinting loci thus providing teh prerequisites for the formation of dsRNA and a potential RNA mediated DNA methylation. In the first part of the project we want to functionally characterize known components of the RNAi machinery in the model organism Dictyostelium and to identify further components. This is based on the previous work on RNAi in Dictyostelium and the identification of three RdRP and two dicer homologs. In the second part of the project we would like to enter the TGS field by analyzing the function of a recently identified Dictyostelium methyltransferase (Dnmt2 homolog), especially in relation to small dsRNAs. In the frame of the Schwerpunktprogramm, data from both projects will be applied in and compared to other model systems (human cell culture, plants, Drosophila).