title: Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL).
abstract: Histidyl-tRNA synthetase catalyses the covalent ligation of histidine to its cognate tRNA as an early step in protein biosynthesis. In humans, the histidyl-tRNA synthetase gene (HARS) is oriented opposite of a synthetase-like gene (HARSL) that bears striking homology to HARS. In this report, we describe the genomic organization of the HARS/HARSL locus and map multiple transcripts originating from a bi-directional promoter controlling the differential expression of these genes. The HARS and HARSL genes each contain 13 exons with strong structural and sequence homology over exons 3-12. HARS transcripts originate from two distinct promoters; a cluster of short transcripts map 15-65 bp upstream of the HARS ORF while a single, longer transcript (352 bp 5(')-UTR) maps to a distal promoter. Similarly, multiple HARSL transcripts (mapping 10-198 bp upstream of its ORF) are produced by the shared bi-directional promoter. Human and rodent HARS/HARSL loci are homologous and support a model of inverted gene duplication to explain the emergence of HARSL during mammalian evolution.
authors.affiliation: Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD 20892, USA. ohanlon@niehs.nih.gov
authors.forename: Terrance P
authors.initials: TP
authors.lastname: O'Hanlon
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D015894:Genome, Human; D006643:Histidine-tRNA Ligase / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D014158:Transcription, Genetic
chemical_list: D006643:Histidine-tRNA Ligase