Research project The exosome: roles in chromatin regulation and DNA repair
The project aims at understanding the molecular mechanisms by which degradation of ncRNAs by the exosome contributes to the organization of the genome and to efficient DNA repair.
Eukaryotic genomes produce a large variety of non-coding RNAs (ncRNAs) some of which are the result of pervasive transcription of genomic regions that were considered “silent”. Pervasive ncRNAs are typically unstable because they are rapidly degraded by the RNA exosome, a multiprotein complex that has ribonucleolytic activity. Because of their low abundance, rapid turnover and lack of conserved structural features, many pervasive ncRNAs have been considered to be non-functional noise. However, our work on the RNA exosome has revealed that some pervasive ncRNAs interact with the chromatin and affect important processes such as heterochromatin folding and gene expression. We have also detected ncRNA synthesis and degradation at DNA double-strand breaks (DSBs) and findings from several labs, including ours, point to important roles for RNA in DNA repair. The project aims at understanding the molecular mechanisms by which degradation of ncRNAs by the exosome contributes to the organization of the genome and to efficient DNA repair. We also intend to investigate the potential of the exosome as a target for anticancer therapy and, to this end, we aim at identifying small molecule inhibitors of exosome activity.