adenosine-to-inosine tRNA-editing enzyme that can perform C-to-U deamination of DNA

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 19; pp. 7821 - 7826
• Main Authors: Rubio, Mary Anne T, Pastar, Irena, Gaston, Kirk W, Ragone, Frank L, Janzen, Christian J, Cross, George A.M, Papavasiliou, F. Nina, Alfonzo, Juan D
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08-05-2007; National Acad Sciences
• Subjects: Adenosine; Adenosine - metabolism; Adenosine Deaminase - physiology; Amino Acid Sequence; Anticodon; Bacteria; Base Sequence; Biochemistry; Biological Sciences; Cell Line; Codons; Cytidine - metabolism; Cytidine Deaminase - physiology; Deamination; Deoxyribonucleic acid; DNA; Enzymes; Genetic mutation; Genetic vectors; Inosine - metabolism; Molecular Sequence Data; Nucleotides; Polynucleotides; RNA; RNA Editing; RNA Interference; Transfer RNA; Trypanosoma brucei; Uridine - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0702394104

Adenosine-to-inosine editing in the anticodon of tRNAs is essential for viability. Enzymes mediating tRNA adenosine deamination in bacteria and yeast contain cytidine deaminase-conserved motifs, suggesting an evolutionary link between the two reactions. In trypanosomatids, tRNAs undergo both cytidine-to-uridine and adenosine-to-inosine editing, but the relationship between the two reactions is unclear. Here we show that down-regulation of the Trypanosoma brucei tRNA-editing enzyme by RNAi leads to a reduction in both C-to-U and A-to-I editing of tRNA in vivo. Surprisingly, in vitro, this enzyme can mediate A-to-I editing of tRNA and C-to-U deamination of ssDNA but not both in either substrate. The ability to use both DNA and RNA provides a model for a multispecificity editing enzyme. Notably, the ability of a single enzyme to perform two different deamination reactions also suggests that this enzyme still maintains specificities that would have been found in the ancestor deaminase, providing a first line of evidence for the evolution of editing deaminases.