AARS

Summary

Gene Symbol: AARS
Description: alanyl-tRNA synthetase
Alias: CMT2N, EIEE29, alanine--tRNA ligase, cytoplasmic, alaRS, alanine tRNA ligase 1, cytoplasmic, alanyl-tRNA synthetase, cytoplasmic, renal carcinoma antigen NY-REN-42
Species: human
Products:     AARS

Top Publications

  1. Englert M, Vargas Rodriguez O, Reynolds N, Wang Y, Soll D, Umehara T. A genomically modified Escherichia coli strain carrying an orthogonal E. coli histidyl-tRNA synthetase•tRNAHis pair. Biochim Biophys Acta. 2017;1861:3009-3015 pubmed publisher
    Development of new aminoacyl-tRNA synthetase (aaRS)•tRNA pairs is central for incorporation of novel non-canonical amino acids (ncAAs) into proteins via genetic code expansion (GCE)...
  2. Kumar M, Kumar S, Dimkovikj A, Baykal L, Banton M, Outlaw M, et al. Zinc is the molecular "switch" that controls the catalytic cycle of bacterial leucyl-tRNA synthetase. J Inorg Biochem. 2015;142:59-67 pubmed publisher
    The Escherichia coli (E. coli) leucyl-tRNA synthetase (LeuRS) enzyme is part of the aminoacyl-tRNA synthetase (aaRS) family. LeuRS is an essential enzyme that relies on specialized domains to facilitate the aminoacylation reaction...
  3. Kubyshkin V, Acevedo Rocha C, Budisa N. On universal coding events in protein biogenesis. Biosystems. 2017;: pubmed publisher
    ..It starts with amino acid activation by aminoacyl tRNA synthetases (aaRS) followed by matching with the acceptor units of their cognate tRNAs ("operational RNA code") and ribosomal codon-..
  4. Götz A, Tyynismaa H, Euro L, Ellonen P, Hyötyläinen T, Ojala T, et al. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am J Hum Genet. 2011;88:635-42 pubmed publisher
    ..Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. ..
  5. McLaughlin H, Sakaguchi R, Giblin W, Wilson T, Biesecker L, Lupski J, et al. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N). Hum Mutat. 2012;33:244-53 pubmed publisher
    ..variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined...
  6. Caetano Anolles G, Kim K, Caetano Anolles D. The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis. J Mol Evol. 2012;74:1-34 pubmed publisher
    ..Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein ..
  7. Sun L, Song Y, Blocquel D, Yang X, Schimmel P. Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS. Proc Natl Acad Sci U S A. 2016;113:14300-14305 pubmed
    ..b>AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans ..
  8. Sun L, Gomes A, He W, Zhou H, Wang X, Pan D, et al. Evolutionary Gain of Alanine Mischarging to Noncognate tRNAs with a G4:U69 Base Pair. J Am Chem Soc. 2016;138:12948-12955 pubmed
    ..Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mispairing alanine onto nonalanyl-tRNAs including tRNACys...
  9. Simons C, Griffin L, Helman G, Golas G, Pizzino A, Bloom M, et al. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am J Hum Genet. 2015;96:675-81 pubmed publisher
    ..associated with an autosomal-dominant inherited form of axonal neuropathy, Charcot-Marie-Tooth disease type 2N (CMT2N)...
  10. Liu Y, Satz J, Vo M, Nangle L, Schimmel P, Ackerman S. Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy. Proc Natl Acad Sci U S A. 2014;111:17570-5 pubmed publisher
    ..Reduced translational fidelity, caused by a hypomorphic mutation in the editing domain of alanyl-tRNA synthetase (AlaRS), resulted in accumulation of misfolded proteins in specific mouse neurons...

Detail Information

Publications36

  1. Englert M, Vargas Rodriguez O, Reynolds N, Wang Y, Soll D, Umehara T. A genomically modified Escherichia coli strain carrying an orthogonal E. coli histidyl-tRNA synthetase•tRNAHis pair. Biochim Biophys Acta. 2017;1861:3009-3015 pubmed publisher
    Development of new aminoacyl-tRNA synthetase (aaRS)•tRNA pairs is central for incorporation of novel non-canonical amino acids (ncAAs) into proteins via genetic code expansion (GCE)...
  2. Kumar M, Kumar S, Dimkovikj A, Baykal L, Banton M, Outlaw M, et al. Zinc is the molecular "switch" that controls the catalytic cycle of bacterial leucyl-tRNA synthetase. J Inorg Biochem. 2015;142:59-67 pubmed publisher
    The Escherichia coli (E. coli) leucyl-tRNA synthetase (LeuRS) enzyme is part of the aminoacyl-tRNA synthetase (aaRS) family. LeuRS is an essential enzyme that relies on specialized domains to facilitate the aminoacylation reaction...
  3. Kubyshkin V, Acevedo Rocha C, Budisa N. On universal coding events in protein biogenesis. Biosystems. 2017;: pubmed publisher
    ..It starts with amino acid activation by aminoacyl tRNA synthetases (aaRS) followed by matching with the acceptor units of their cognate tRNAs ("operational RNA code") and ribosomal codon-..
  4. Götz A, Tyynismaa H, Euro L, Ellonen P, Hyötyläinen T, Ojala T, et al. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am J Hum Genet. 2011;88:635-42 pubmed publisher
    ..Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. ..
  5. McLaughlin H, Sakaguchi R, Giblin W, Wilson T, Biesecker L, Lupski J, et al. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N). Hum Mutat. 2012;33:244-53 pubmed publisher
    ..variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined...
  6. Caetano Anolles G, Kim K, Caetano Anolles D. The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis. J Mol Evol. 2012;74:1-34 pubmed publisher
    ..Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein ..
  7. Sun L, Song Y, Blocquel D, Yang X, Schimmel P. Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS. Proc Natl Acad Sci U S A. 2016;113:14300-14305 pubmed
    ..b>AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans ..
  8. Sun L, Gomes A, He W, Zhou H, Wang X, Pan D, et al. Evolutionary Gain of Alanine Mischarging to Noncognate tRNAs with a G4:U69 Base Pair. J Am Chem Soc. 2016;138:12948-12955 pubmed
    ..Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mispairing alanine onto nonalanyl-tRNAs including tRNACys...
  9. Simons C, Griffin L, Helman G, Golas G, Pizzino A, Bloom M, et al. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am J Hum Genet. 2015;96:675-81 pubmed publisher
    ..associated with an autosomal-dominant inherited form of axonal neuropathy, Charcot-Marie-Tooth disease type 2N (CMT2N)...
  10. Liu Y, Satz J, Vo M, Nangle L, Schimmel P, Ackerman S. Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy. Proc Natl Acad Sci U S A. 2014;111:17570-5 pubmed publisher
    ..Reduced translational fidelity, caused by a hypomorphic mutation in the editing domain of alanyl-tRNA synthetase (AlaRS), resulted in accumulation of misfolded proteins in specific mouse neurons...
  11. Zhao Z, Hashiguchi A, Hu J, Sakiyama Y, Okamoto Y, Tokunaga S, et al. Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy. Neurology. 2012;78:1644-9 pubmed publisher
    ..2677G>A (p.D893N) of alanyl-tRNA synthetase (AARS), which was not found in the 4 unaffected members and control subjects...
  12. Roberts L, Nossek C, Greenberg L, Ramesar R. Stargardt macular dystrophy: common ABCA4 mutations in South Africa--establishment of a rapid genetic test and relating risk to patients. Mol Vis. 2012;18:280-9 pubmed
    ..a mechanism for identifying common disease-causing mutations in subjects with ABCA4-associated retinopathies (AARs)...
  13. Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S. Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex. Biochem Biophys Res Commun. 2002;291:158-64 pubmed
    ..These data suggest that a systematic interaction network may exist between mammalian ARSs and EF-1 subunits probably to enhance the efficiency of in vivo protein synthesis. ..
  14. Yakobov N, Debard S, Fischer F, Senger B, Becker H. Cytosolic aminoacyl-tRNA synthetases: Unanticipated relocations for unexpected functions. Biochim Biophys Acta. 2017;: pubmed publisher
    ..signaling pathways that trigger their relocation and the new functions associated with these relocating cytosolic aaRS. Finally, given that these relocating pools of cytosolic aaRSs participate to a wide range of cellular pathways ..
  15. Shiba K, Ripmaster T, Suzuki N, Nichols R, Plotz P, Noda T, et al. Human alanyl-tRNA synthetase: conservation in evolution of catalytic core and microhelix recognition. Biochemistry. 1995;34:10340-9 pubmed
    ..Thus, the region of close sequence similarity may be a consequence of strong selective pressure to conserve the acceptor helix G3:U70 base pair as an RNA signal for alanine. ..
  16. Grube C, Roy H. A continuous assay for monitoring the synthetic and proofreading activities of multiple aminoacyl-tRNA synthetases for high-throughput drug discovery. RNA Biol. 2017;: pubmed publisher
    ..The aaRS editing site hydrolyzes misacylated products formed when a non-cognate amino acid is used during tRNA charging...
  17. Dohrn M, Glöckle N, Mulahasanovic L, Heller C, Mohr J, Bauer C, et al. Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. J Neurochem. 2017;143:507-522 pubmed publisher
    ..pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency...
  18. Wang L. Engineering the Genetic Code in Cells and Animals: Biological Considerations and Impacts. Acc Chem Res. 2017;50:2767-2775 pubmed publisher
    ..Orthogonal components including tRNA and aminoacyl-tRNA synthetase (aaRS) are expressed in live cells to decode a unique codon (often the amber stop codon UAG) as the desired Uaa...
  19. Vijayakumar R, Tripathi T. Soluble expression and purification of a full-length asparaginyl tRNA synthetase from Fasciola gigantica. Protein Expr Purif. 2018;143:9-13 pubmed publisher
    ..It causes fascioliasis that infects the liver of various mammals, including humans. Aminoacyl tRNA synthetases (AARS) catalyze the first step of protein synthesis...
  20. Masoudi M, Derakhshan N, Ghaffarpasand F, Sadeghpour T. Management of Pediatric Atlantoaxial Rotatory Subluxation with a Simple Handmade Cervical Traction Device: Doing More with Less. World Neurosurg. 2017;106:355-358 pubmed publisher
    To introduce a novel traction device for management of pediatric atlanto-axial rotatory subluxation (AARS) in source limiting areas. Atlanto-axial (C1-C2) joint is accountable for up to two third of total axial craniocervical rotation...
  21. He X, Li S, Liu B, Susperreguy S, Formoso K, Yao J, et al. Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries. Proc Natl Acad Sci U S A. 2017;114:E4582-E4591 pubmed publisher
    ..subjected to 9-h hypoxia followed by 6-h reoxygenation (H/R), and analyzing changes occurring in areas-at-risk (AARs) of murine hearts subjected to a 30-min ischemia followed by 24-h reperfusion (I/R) protocol, we found: (i) ..
  22. Carter C, Wills P. Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding. Mol Biol Evol. 2017;: pubmed publisher
    ..thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS)...
  23. Nakayama T, Wu J, Galvin Parton P, Weiss J, Andriola M, Hill R, et al. Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive syndrome of progressive microcephaly, hypomyelination, and epileptic encephalopathy. Hum Mutat. 2017;38:1348-1354 pubmed publisher
    ..Although alanyl-tRNA synthetase (AARS) is a synthetase implicated in a wide range of neurological disorders from Charcot-Marie-Tooth disease to infantile ..
  24. Bánsági B, Antoniadi T, Burton Jones S, Murphy S, McHugh J, Alexander M, et al. Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland. J Neurol. 2015;262:1899-908 pubmed publisher
    ..To date six families have been reported worldwide with dominant missense alanyl-tRNA synthetase (AARS) mutations leading to clinically heterogeneous axonal neuropathies...
  25. Lovato M, Chihade J, Schimmel P. Translocation within the acceptor helix of a major tRNA identity determinant. EMBO J. 2001;20:4846-53 pubmed
    ..translocated G:U and the adjacent G3:C70 are major determinants for recognition by Dm mt alanyl-tRNA synthetase (AlaRS). Additionally, G:U at the 3:70 position serves as an anti-determinant for Dm mt AlaRS...
  26. Nichols R, Pai S, Ge Q, Targoff I, Plotz P, Liu P. 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. Genomics. 1995;30:131-2 pubmed
  27. Ripmaster T, Shiba K, Schimmel P. Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast cytoplasmic alanine enzyme replaced by human polymyositis serum antigen. Proc Natl Acad Sci U S A. 1995;92:4932-6 pubmed
    ..U70 system of recognition is sufficient to yield accurate aminoacylation in vivo across wide species distances. ..
  28. Motley W, Griffin L, Mademan I, Baets J, De Vriendt E, De Jonghe P, et al. A novel AARS mutation in a family with dominant myeloneuropathy. Neurology. 2015;84:2040-7 pubmed publisher
    ..304G>C (p.Gly102Arg) in the alanyl-tRNA synthetase (AARS) gene; this allele was not identified in unaffected individuals or control samples...
  29. Andrade V, Guerra M, Jardim C, Melo F, Silva W, Ortega J, et al. Nucleoplasmic calcium regulates cell proliferation through legumain. J Hepatol. 2011;55:626-635 pubmed publisher
    ..Increased expression of LGMN may be involved in liver carcinogenesis. ..
  30. Ferro I, Liebeton K, Ignatova Z. Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis. J Mol Biol. 2017;429:3102-3112 pubmed publisher
    ..level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS)...
  31. Latour P, Thauvin Robinet C, Baudelet Méry C, Soichot P, Cusin V, Faivre L, et al. A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet. 2010;86:77-82 pubmed publisher
    ..Arg329His), affecting a totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA synthetase (AlaRS)...
  32. Zheng Y, Addy P, Mukherjee R, Chatterjee A. Defining the current scope and limitations of dual noncanonical amino acid mutagenesis in mammalian cells. Chem Sci. 2017;8:7211-7217 pubmed publisher
    ..It would require the use of two different engineered aminoacyl-tRNA synthetase (aaRS)/tRNA pairs, each suppressing a distinct nonsense codon, and which cross-react neither with each other, nor with ..
  33. Restelli L, Marques A, Savoini G, Invernizzi G, Carisetti M, Lecchi C, et al. Saturated or unsaturated fat supplemented maternal diets influence omental adipose tissue proteome of suckling goat-kids. Res Vet Sci. 2017;: pubmed publisher
    ..Stearic acid induces changes in a higher number of proteins when compared to fish oil. Eleven proteins, namely AARS, ECl1, PMSC2, CP, HSPA8, GPD1, RPL7, OGDH, RPL24, FGA and RPL5 were decreased in ST-kids only...
  34. Rathnayake U, Wood W, Hendrickson T. Indirect tRNA aminoacylation during accurate translation and phenotypic mistranslation. Curr Opin Chem Biol. 2017;41:114-122 pubmed publisher
    The fact that most bacteria do not contain a full set of aminoacyl-tRNA synthetases (aaRS) is often underappreciated...
  35. Francklyn C, Schimmel P. Aminoacylation of RNA minihelices with alanine. Nature. 1989;337:478-81 pubmed
    ..Alanine incorporation requires a single G.U base pair, and occurs in helices that otherwise differ significantly in sequence. Aminoacylation can be achieved with only seven base pairs in the helix. ..