title: An adenosine-to-inosine tRNA-editing enzyme that can perform C-to-U deamination of DNA.
abstract: 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.
authors.affiliation: Department of Microbiology and the Ohio State RNA Group, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mary Anne T
authors.initials: MA
authors.lastname: Rubio
authors.forename: Irena
authors.initials: I
authors.lastname: Pastar
authors.forename: Kirk W
authors.initials: KW
authors.lastname: Gaston
authors.forename: Frank L
authors.initials: FL
authors.lastname: Ragone
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Janzen
authors.forename: George A M
authors.initials: GA
authors.lastname: Cross
authors.forename: F Nina
authors.initials: FN
authors.lastname: Papavasiliou
authors.forename: Juan D
authors.initials: JD
authors.lastname: Alfonzo
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000502:physiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003562:Cytidine / Q000378:metabolism; D003564:Cytidine Deaminase / Q000502:physiology*; D003641:Deamination; D007288:Inosine / Q000378:metabolism; D008969:Molecular Sequence Data; D017393:RNA Editing; D034622:RNA Interference; D014529:Uridine / Q000378:metabolism
chemical_list: D007288:Inosine; D003562:Cytidine; D000243:Adenosine Deaminase; D003564:Cytidine Deaminase; D000241:Adenosine; D014529:Uridine