Grant: Operating Grant

According to the central dogma of biology, genes encoded by DNA are transcribed into RNAs, which are then translated into proteins. Today, we know that RNA transcripts undergo numerous maturations steps to yield translatable RNAs. Typically, post-transcriptional RNA processing includes removal of introns and addition of a tail consisting of the base A. In addition, the sequence of some transcripts is changed ('RNA editing') or pasted together from distinct RNAs ('trans-splicing'). Several such instances have been observed in human, and they have been linked to the generation of enzyme isoforms in specialized tissue cells. Yet, the underlying molecular mechanisms of RNA editing and trans-splicing are not fully understood. We propose here to investigate RNA editing and trans-splicing in eukaryotic microbes - diplonemids - where these otherwise rare events are the rule. This work has potential long-term impacts on health research. First, dissection of the cellular machineries catalyzing these processes may expand the molecular tools for treating hereditary disorders at the RNA level. Second, these studies may also shed light on the evolution of the pathogenic microbes Leishmania and Trypanosoma, the causative agents of leishmaniasis and Chagas disease, since diplonemids are their free-living sistergroup.