We are interested in understanding the different functions of the RNA exosome in the nucleus. We have several projects related to the RNA exosome, including RNA degradation and chromain associated RNAs, the role of the RNA exosome in transcription and the role of the RNA exosome in genomic instability.
For the role of chromatin-associated RNA (caRNA) in the regulation of chromatin compaction. We have already carried out RNAi experiments to deplete exosome subunits in S2 cells (Drosophila melanogaster) and we carried out RNA-seq experiments to detect caRNAs that are exosome-sensitive. In order to investigate the biological relevance of the impaired abundances of caRNAs, we have performed a ATAC-seq to correlate RNA levels with chromatin compaction genome-wide.
Derived from caRNA project, we observed that snoRNAs are enriched in chromatin. We are investigating the role of a specific snoRNA, snoRNA:U3:9B in chromatin compaction regulation. To do this, we use an infection model that induces the snoRNA:U3:9B. We have generated KO flies for this snoRNA, and we have performed a chromatin accessibility experiment (ATAC-seq) in no infection and infection conditions in three different fly genotypes (control, deletion1, deletion3) to establish a functional link between the immune response in Drosophila, and the regulation that snoRNA:U3:9B exerts.
We also have several pieces of evidence highlighting that the RNA exosome and particularly the catalytic subunit DIS3 is required for transcription recovery following UV-damages. Independently on UV-damages, our data suggests that DIS3 has a function in general transcription, specifically in the transition from initiation to elongation. We hypothesize that an accumulation of RNA transcripts in the absence of DIS3, is restricting an efficient transition into elongation.