The organization of the DNA into chromatin and the maintenance of the integrity of the genome are essential biological processes. Research from many laboratories has provided knowledge about the proteins that are responsible for these processes. More recently, we have learned that not only proteins but also RNAs play important roles in genome organization, gene regulation and DNA repair. Eukaryotic genomes are transcribed to a much larger extent than initially anticipated, and different types of non-coding RNAs (ncRNAs) have been identified. Some of these ncRNAs regulate chromatin structure and gene expression, and their biogenesis and turnover depend on the activity of the exosome, an enzymatic complex that is responsible for the processing and degradation of many RNAs in eukaryotic cells. Our research addresses the following specific questions:

• chromatin associated RNAs, their functions and the roles of the exosome in maintaining chromatin homeostasis
• RNA synthesis and degradation at DNA double-strand breaks
• non-canonical roles for snoRNAs in chromatin regulation and gene expression

We use the fruit fly Drosophila melanogaster as a model organism to study chromatin-associated ncRNAs and to investigate the roles of snoRNAs in chromatin regulation and gene expression. We use mammalian cell systems for studies of DNA repair. Our research combines biochemistry, molecular biology, genetics, cell biology and high-throughput methods such as RNA-seq, ChIP-seq and ATAC-seq.

Our research provides fundamental knowledge about basic genetic processes. Our work is also interesting from a biomedical perspective. Novel strategies to treat human diseases, including cancer and neurological disorders, target chromatin regulatory pathways and DNA repair factors. The exosome itself has been linked to human diseases and proposed as a possible target for therapeutic intervention. Thus, understanding the mechanisms of chromatin regulation and exosome function is of outmost strategic relevance.

Keywords: 
Non-coding RNA, exosome, RNA degradation, DNA repair, chromatin, eukaryotic gene expression