The major goal of my research is to determine the mechanisms by which the African protozoan parasite Trypanosoma brucei is able to differentially edit several mitochondrial transcripts between the two major developmental forms of the parasite that are found in the tsetse fly insect vector and in the mammalian bloodstream.
RNA editing in Trypanosoma brucei is a fascinating and highly complex biological process. For several of the mitochondrial mRNAs, the nucleotide sequences do not match with the DNA sequences of the mitochondrial genes from which they are transcribed. This is due to the fact that T. brucei edits 12 out of the 18 mitochondrial transcripts by uridine insertion/deletion. This can potentially yield a final mRNA molecule that looks drastically different than the initial mitochondrial gene. This extensive editing also yields a translatable open reading frame that can be translated into proteins that are typically subunits of the respiratory complexes and the mitochondrial ribosomes.
Previous research shows that the mitochondrial mRNAs and the guide RNAs that facilitate mRNA editing are all transcribed and present in comparable amounts in both the procyclic form (insect) and bloodstream form (mammal), but the editing status of these mitochondrial mRNAs differs between the developmental forms. The mechanism by which this occurs is still unknown, and it is the goal of my research to understand the protein-protein and RNA-protein interactions that are necessary to maintain proper editing in procyclic and bloodstream parasites and the mechanisms to switch the developmental profile of editing in T. brucei.
Joseph T. Smith Jr., PhD
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