Disease relevance of AARS

• Aminoacyl-tRNA synthetases (AARS) are a family of heterogenous enzymes responsible for protein synthesis and whose secondary functions include a role in autoimmune myositis [1].
• In Brugia malayi, the gene for asparaginyl-tRNA synthetase (AsnRS), a class II AARS, previously has been identified as a multicopy gene encoding an immunodominant antigen in the serum of humans with lymphatic filariasis [2].
• In this work, we examined a fragment of Escherichia coli alanyl-tRNA synthetase, which catalyzes aminoacyl adenylate formation but is virtually inactive for catalysis of RNA microhelix aminoacylation [3].
• The signatures in succinyl-CoA synthetase, cytochrome oxidase I, alanyl-tRNA synthetase, and MutS proteins are found in all alpha-proteobacteria, except the Rickettsiales, indicating that this group has diverged prior to the introduction of these signatures [4].
• Antibodies to ATS (anti-PL-12) represent the most common reactivity that defines the antisynthetase syndrome, which is typically expressed as polymyositis, dermatomyositis and interstitial lung disease (ILD) [5].

High impact information on AARS

• Sera of the PL-12 specificity contain separate antibodies reacting with alanyl-tRNA synthetase and alanine tRNA (tRNAAla) [6].
• Aminoacylation experiments identify the antigens as alanyl-tRNA synthetase and its corresponding tRNAs, tRNAAla [7].
• Autoantibodies against alanyl-tRNA synthetase and tRNAAla coexist and are associated with myositis [7].
• Thus, tRNA-dependent editing by AlaRS may have been critical for making the genetic code sufficiently accurate to generate the tree of life [8].
• Here, we report crystal structures of an active fragment of Aquifex aeolicus alanyl-tRNA synthetase complexed, separately, with Mg2+-ATP, alanine, glycine, and serine [9].

Biological context of AARS

• Human alanyl-tRNA synthetase: conservation in evolution of catalytic core and microhelix recognition [10].
• AARS catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid [11].
• A hamster temperature-sensitive alanyl-tRNA synthetase mutant causes degradation of cell-cycle related proteins and apoptosis [12].
• We searched the Filarial Genome Project database to identify the number and amino acid specificity of B. malayi AARS cDNAs to gain insight into the role of different AARS in filaria [2].
• Here we report the observation of marked differences in mRNA secondary structure associated with SNPs in the coding regions of two human mRNAs: alanyl tRNA synthetase and replication protein A, 70-kDa subunit (RPA70) [13].

Anatomical context of AARS

• Currently, 818 AARS primary structures have been reported from archaebacteria, eubacteria, mitochondria, chloro-plasts and eukaryotic cells [14].
• The updated database contains 1047 AARS primary structures from archaebacteria, eubacteria, mitochondria, chloroplasts and eukaryotic cells [15].

Associations of AARS with chemical compounds

• Loss of the mutated alanyl-tRNA synthetase was inhibited by a ubiquitin-dependent proteasome inhibitor, MG132, and by a protein-synthesis inhibitor, cycloheximide [12].
• In order to elucidate the substrate specificity of alanyl-tRNA synthetase, 5'-O-[N-(L-alanyl)sulfamoyl]adenosine (Ala-SA), an analogue of alanyl-AMP, was chemically synthesized [16].

Other interactions of AARS

• Localization of two human autoantigen genes by PCR screening and in situ hybridization--glycyl-tRNA synthetase locates to 7p15 and alanyl-tRNA synthetase locates to 16q22 [17].
• The AARS and HADS were used as screening questionnaires for ADHD and anxiety behaviour, respectively [18].
• The relative level of AsnRS transcribed in adult female B. malayi was compared to the levels of a low abundance and medium abundance AARS by quantitative real-time RT-PCR [2].
• The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports [19].

References