Genomic clustering of tRNA-specific adenosine deaminase ADAT1 and two tRNAsynthetases

Human tRNA-specific adenosine deaminase (hADAT1) specifically convects A37 in the anticodon loop of human tRNA(Ala) to inosine via a hydrolytic deamin ation mechanism. The enzyme is related to a family of RNA editing enzymes ( ADARs) specific for pre-mRNA, and it has been cloned based on its sequence homology to the catalytic domain of ADARs. In the present study we have ana lyzed the 5 ' -flanking sequence of the murine ADAT1 gene, revealing that t he first transcribed exon is located 1.1 hb downstream from the polyadenyla tion site of lysyl tRNA synthetase (KARS), The close proximity is conserved in the human genome with an intergenic distance of 5.5 hb. We determined t he complete cDNA Sequence as well as exon/intron organization of murine KAR S, Significant sequence similarities between KARS and ADAT1 are apparent wi thin their substrate interaction domains. Radiation hybrid panel analysis m apped human ADAT1 and human KARS to region q22.2-22.3 of Chromosome (Chr) 1 6 with alanyl tRNA synthetase (AARS) positioned centromeric to the KARS and ADAT1 genes. 16q22-24 has recently been recognized as a susceptibility can didate locus for several autoimmune inflammatory diseases, The clustering o f three tRNA specific genes, of which two are specific for rTNA(Ala), may i ndicate their evolutionary relatedness or common factors Involved in regula ting their expression.