Project description:Indisulam is an abandoned drug that acts as a molecular glue, inducing degradation of splicing factor RBM39 through interaction with CRL4DCAF15. We combined indisulam with sphinx 31 (a splicing factor inhibitor) and evaluated their combined activity in inducing splicing errors.
Project description:Analyses of new genomic, transcriptomic or proteomic data commonly result in trashing many unidentified data escaping the ‘canonical’ DNA-RNA-protein scheme. Testing systematic exchanges of nucleotides over long stretches produces inversed RNA pieces (here named “swinger” RNA) differing from their template DNA. These may explain some trashed data. Here analyses of genomic, transcriptomic and proteomic data of the pathogenic Tropheryma whipplei according to canonical genomic, transcriptomic and translational 'rules' resulted in trashing 58.9% of DNA, 37.7% RNA and about 85% of mass spectra (corresponding to peptides). In the trash, we found numerous DNA/RNA fragments compatible with “swinger” polymerization. Genomic sequences covered by «swinger» DNA and RNA are 3X more frequent than expected by chance and explained 12.4 and 20.8% of the rejected DNA and RNA sequences, respectively. As for peptides, several match with “swinger” RNAs, including some chimera, translated from both regular, and «swinger» transcripts, notably for ribosomal RNAs. Congruence of DNA, RNA and peptides resulting from the same swinging process suggest that systematic nucleotide exchanges increase coding potential, and may add to evolutionary diversification of bacterial populations.