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

Abstract.

Human tRNA-specific adenosine deaminase (hADAT1) specifically converts A37 in the anticodon loop of human tRNA^Ala to inosine via a hydrolytic deamination 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 analyzed the 5′-flanking sequence of the murine ADAT1 gene, revealing that the first transcribed exon is located 1.1 kb downstream from the polyadenylation site of lysyl tRNA synthetase (KARS). The close proximity is conserved in the human genome with an intergenic distance of 5.5 kb. We determined the complete cDNA sequence as well as exon/intron organization of murine KARS. Significant sequence similarities between KARS and ADAT1 are apparent within their substrate interaction domains. Radiation hybrid panel analysis mapped human ADAT1 and human KARS to region q22.2–22.3 of Chromosome (Chr) 16 with alanyl tRNA synthetase (AARS) positioned centromeric to the KARS and ADAT1 genes. 16q22–24 has recently been recognized as a susceptibility candidate locus for several autoimmune inflammatory diseases. The clustering of three tRNA specific genes, of which two are specific for tRNA^Ala, may indicate their evolutionary relatedness or common factors involved in regulating their expression.