TAD1P, A YEAST TRANSFER-RNA-SPECIFIC ADENOSINE-DEAMINASE, IS RELATED TO THE MAMMALIAN PRE-MESSENGER-RNA EDITING ENZYMES ADAR1 AND ADAR2

We have identified an RNA-specific adenosine deaminase (termed Tad1p/s cADAT1) from Saccharomyces cerevisiae that selectively converts adenos ine at position 37 of eukaryotic tRNA(Ala) to inosine. The activity of purified recombinant Tad1p depends on the conformation of its tRNA su bstrate and the enzyme was found to be inactive on all other types of RNA tested. Mutant strains in which the TAD1 gene is disrupted are via ble but lack Tad1p enzyme activity and their tRNA(Ala) is not modified at position A(37). Transformation of the mutant cells with the TAD1 g ene restored enzyme activity. Tad1p has significant sequence similarit y with the mammalian editing enzymes which act on specific precursor-m RNAs and on long double-stranded RNA. These findings suggest an evolut ionary link between pre-mRNA editing and tRNA modification.