Friedrich Miescher Institute for Biomedical Research
Maulbeerstrasse 66
4058 Basel, Switzerland
Email: marc.buehler@fmi.ch
Secretary: Dawn Hammond
Phone: +41 61 697 66 51
Crosstalk between RNA turnover and chromatin-dependent gene silencing mechanisms
Over the last few years, there has been a convergence of two seemingly disparate fields of study: heterochromatic gene silencing and RNA turnover. In particular, data from a variety of organisms have shown that the assembly of repetitive DNA elements into heterochromatic domains, such as those found in eukaryotic centromeres and telomeres, also requires the activity of proteins involved in the RNA interference (RNAi) pathway. Because of their critical role in basic cellular functions, malfunctioning heterochromatin assembly or RNAi leads to a number of human diseases including cancer. Thus, the interface between RNA turnover and chromatin biology is an exciting arena for research, one in which understanding its molecular mechanism could yield promising new drug targets, or gene therapy tools for the treatment of human disease.
Biochemical and genetic analyses improved our understanding of how the RNAi pathway contributes to heterochromatin assembly in the fission yeast Schizosaccharomyces pombe and challenged the longstanding paradigm that heterochromatin is an inert, transcriptionally inactive structure. Recent work has demonstrated that silencing of genes inserted into heterochromatin and heterochromatic repeat elements itself might be mediated by RNAi as well as exosome mediated co-transcriptional processing events, rather than by shutting off transcription. This novel mode of gene silencing is referred to as "Co-Transcriptional Gene Silencing" (CTGS) and its mechanistic details remain largely unknown. Our goal is to completely understand the mechanistic details of CTGS, which will further our understanding of the role of RNA turnover pathways in controlling eukaryotic gene expression. We will also continue analyzing the RNAi machinery by employing parallel genetic, biochemical, molecular biological, advanced live cell imaging and proteomic approaches.
