Disease relevance of HARS

• Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in approximately 25% of patients with polymyositis or dermatomyositis [1].
• We randomly selected 150 case patients and 150 control patients whose AIDS diagnosis was made during 1994 to 1996 (male:female, 2:1) from among 19,238 persons reported to the NYC Health Department HIV/AIDS Reporting System (HARS) [2].
• Epitope studies indicate that histidyl-tRNA synthetase is a stimulating antigen in idiopathic myositis [3].
• In Lactococcus lactis there is a protein, HisZ, in the histidine-biosynthetic operon that exhibits significant sequence identity with histidyl-tRNA synthetase (HisRS) but does not aminoacylate tRNA [4].
• We now report that mammalian GCN2 is specifically activated in vitro upon binding of two nonadjacent regions of the Sindbis virus (SV) genomic RNA to its histidyl-tRNA synthetase-related domain [5].

Psychiatry related information on HARS

• Concomitant psychopathology was monitored through the HARS and HDRS, and level of functioning through the GAS [6].
• Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements [7].
• The clinical scales administered included the Hamilton Anxiety and Depression Rating Scale (HARS and HDRS), the Marks and Mathews Fears and Phobia Scale, Panic-Associated Symptom Scale (PASS), and a panic attack symptoms inventory [8].
• Together, HARS and SHAS collect fairly comprehensive information of risk behaviors from persons with HIV infection and AIDS [9].

High impact information on HARS

• Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity [10].
• Prediction of the histidylation function of the new family of minimalist tRNA-like structures relates to the geometry of resected pseudoknots that allows proper presentation to histidyl-tRNA synthetase of analogues of the histidine identity determinants N-1 and N73 present in tRNAs [11].
• We show here that anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase in the human autoimmune muscle disease polymyositis undergo, in addition to spectrotype broadening and class switching, the sine qua non of an immune response to the target antigen--affinity maturation to that antigen [12].
• The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity [12].
• Critical requirement for professional APCs in eliciting T cell responses to novel fragments of histidyl-tRNA synthetase (Jo-1) in Jo-1 antibody-positive polymyositis [13].

Chemical compound and disease context of HARS

• In this setting, vasoconstriction of the intrarenal vascular system induces marked and often irreversible sodium and water retention, leading to refractory ascites, a progressive rise in plasma creatinine levels and reduction of renal clearances (hepatorenal syndrome, HRS) [14].

Biological context of HARS

• The HARS and HARSL genes each contain 13 exons with strong structural and sequence homology over exons 3-12 [15].
• 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 [15].
• Histidyl-tRNA synthetase catalyses the covalent ligation of histidine to its cognate tRNA as an early step in protein biosynthesis [15].
• Chromosomal localization of human gene for histidyl-tRNA synthetase: clustering of genes encoding aminoacyl-tRNA synthetases on human chromosome 5 [16].
• Epitope mapping of the cloned human autoantigen, histidyl-tRNA synthetase. Analysis of the myositis-associated anti-Jo-1 autoimmune response [17].

Anatomical context of HARS

• Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells) [18].
• Facial atrophy in HIV-related fat redistribution syndrome (HARS) is secondary to atrophy of the subcutaneous fat, but not of the deeper fat pads, as has been described [19].
• This study was done to evaluate whether surgical stress influenced polymorphonuclear (PMN) and monocyte functions in association with serum cortisol and the anxiety score as measured on the HARS Rating Scale [20].
• We have developed an enzyme-linked immunosorbent assay (ELISA) specific for autoantibodies directed against the autoantigen Jo-1 (histidyl-tRNA synthetase) using antigen prepared biochemically from HeLa cells [21].
• Presence of role of the 5SrRNA-L5 protein complex (5SRNP) in the threonyl- and histidyl-tRNA synthetase complex in rat liver cytosol [22].

Associations of HARS with chemical compounds

• Triazolam-treated patients presented significantly more day-time-interdose anxiety than zopiclone as assessed by the weekly HARS and Clinical Global Assessment of Anxiety. Although daytime-interdose anxiety was observed with both drugs, this treatment emergent symptom was more frequent and severe with triazolam [23].
• However, long-term treatment tended (P < 0.06) to increase basal plasma 5-HT concentrations, in covariation with decreases of MADRS (Montgomery-Asberg Depression Rating Scale) and HARS (Hamilton Anxiety Rating Scale) [24].
• Oral treatment with 1800 mg pivagabine lasting 30 days showed in both groups a significant improvement of the psychic state with variations from 50 to 80% of the criteria reported in the Hamilton Rating Scale for Depression (HDRS) and for anxiety (HARS) and in the Self-rating Anxiety Scale (SAS) [25].
• The subunit molecular weight of histidyl-tRNA synthetase is 50,000, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate [26].
• Indeed, the tsBN250 cell line had a single base change--guanine to adenine at the second position of the 362nd codon of hamster histidyl-tRNA-synthetase, converting arginine to histidine [27].

Regulatory relationships of HARS

• A hamster temperature-sensitive G1 mutant, tsBN250 has a single point mutation in histidyl-tRNA synthetase that inhibits an accumulation of cyclin D1 [27].

Other interactions of 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 [15].
• The chromosomal gene (HRS) coding for hamster histidyl-tRNA synthetase, like many other housekeeping genes, lacks many of the features associated with promoters of RNA-polymerase-II-transcribed genes [28].
• TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase [29].
• Later, but not less than 1200 million years ago, the motif spread from histidyl-tRNA synthetase to the C and N terminals of glutamyl- and prolyl-tRNA synthetase, respectively, and then spread further during the evolution of the Chordate lineage to the N terminal of tryptophanyl-tRNA synthetase [30].
• RESULTS: Using the histidyl tRNA synthetase (HtRNAS) gene as a housekeeping gene in the optimised multiplex RT-PCR, a significantly higher level of HERV-K10 gag mRNA expression was found in rheumatoid arthritis than in osteoarthritis (p = 0.01) or in the healthy controls (p = 0.02) [31].

Analytical, diagnostic and therapeutic context of HARS

• The interactions of leucyl- and histidyl-tRNA synthetase with the EF-1 complex were confirmed by immunoprecipitation and in vitro pull-down experiments [32].
• CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase in C-section rates mainly among HIV-infected women in the United States after the release of the meta-analysis and randomized clinical trial results in 1998 [33].
• In addition, the scores on the HDRS, HARS, and Y-BOCS were significantly higher in the study group than in the control group [34].
• Antibody to the Jo-1 antigen (histidyl-tRNA synthetase) is found almost exclusively in myositis patients, usually those with adult PM, but has been found in only 30% of that group by immunodiffusion or other techniques thus far reported [35].
• The increased detection of anti-Jo-1 antibody afforded by the use of the purified antigen, histidyl-tRNA synthetase, in counterimmunoelectrophoresis is demonstrated [36].

References