A Novel Gene Oriented in a Head-to-Head Configuration with the Human Histidyl-tRNA Synthetase (HRS) Gene Encodes an mRNA That Predicts a Polypeptide Homologous to HRS

The human histidyl-tRNA synthetase (HRS) gene encodes an enzyme that catalyzes the esterification of histidine to its cognate tRNA as an early step in protein biosynthesis. Previous reports have described a bidirectional promoter element which coordinates the transcription of both HRS and an unknown mRNA whose gene is oriented in a head-to-head configuration with HRS. We have isolated and characterized a human genomic DNA clone that encodes portions of these oppositely transcribed mRNAs and a putatively full-length cDNA clone (HO3) corresponding to the gene mapping immediately 5′ of HRS. The largest open reading frame within HO3 (1518 bp) shares approximately 75% nucleotide sequence identity with human HRS (1527 bp) and predicts a polypeptide with extensive amino acid sequence homology with the HRS protein (72%). Moreover, amino acid sequence motifs characteristic of class II aminoacyl-tRNA synthetases are conserved within HO3. Despite their similarity, HRS and HO3 have divergent amino-terminal domains which correspond to the first two exons of each gene. RNA blot analysis revealed that HRS (2.0 kb) and HO3 (2.5 kb) exhibit distinct patterns of steady-state mRNA expression among multiple human tissues.