The central dogma of molecular biology states a linear flow of genetic information: DNA to/from RNA to protein. However, recently discovered processes of RNA editing which modify the genetic material during or after transcription expand this paradigm. A dramatic example is the post-transcriptional maturation of mitochondrial mRNAs by the addition and deletion of U residues in trypanosomes, whereby amino acid coding triplets and stop codons are created. Extensive editing in some mRNAs generates over half their mature size, yet a single error in the U-changes yields a frameshift. Trypanosome RNA editing is developmentally regulated and appears to control mitochondrial respiration.
In vitro studies have revealed that high fidelity RNA editing is directed by small transacting guide RNAs (gRNAs), and is catalyzed by a protein complex or editosome containing endonuclease, exonuclease, terminal transferase and RNA ligase. However, several intriguing questions are still unsolved. For instance, how do gRNA-mRNA interactions modulate these enzymatic activities? How is RNA editing controlled during development? What are the RNA signals and the protein factors involved? We are combining biochemical and genetic approaches to address these questions.