Aminoacyl-tRNA synthetases (AARS) are essential proteins found in all living organisms. They form a diverse group of enzymes that ensure the fidelity of transfer of genetic information from the DNA into the protein. 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. Here we summarise the effects of recent studies on this interesting family of multifunctional enzymes.
1. Gesteland, R.F., Cech, T.R. & Atkins, J.F. (eds.) (1999) The RNA World, 2nd edn., 735 pp., Cold Spring Laboratory Press, New York.
2. Keller, W. (1999) In the beginning, there was RNA. Science 285, 668-669.
3. Siatecka, M., Rozek, M., Barciszewski, J. & Mirande, M. (1998) Modular evolution of the GlnRS synthetase family: Rooting of the evolutionary tree between the eubacteria and archaea/eukarya branches. Eur. J. Biochem. 256, 80-87.
4. Szymanski, M. & Barciszewski, J. (2000) Aminoacyl-tRNA synthetases database Y2K. Nucleic Acids Res. 28, 326-328.
5. Koonin, E.V. & Aravind, L. (1998) Re-evaluation of translation machinery evolution. Curr. Biol. 8, R266-R269.
6. Ibba, M., Curnow, A.W. & Soell, D. (1997) Aminoacyl-tRNA synthetases: Different routes to a common goal. Trends Biochem. Sci. 22, 39-42.
7. Shiba, K., Motegi, H. & Schimmel, P. (1997) Maintaining genetic code through adaptations of tRNA synthetases to taxonomic domains. Trends Biochem. Sci. 22, 453-457.
8. Lenhard, B., Orellana, O., Ibba, M. & Weygand-Durasevic, I. (1999) tRNA recognition and evolution of determinants in seryl-tRNA synthesis. Nucleic Acids Res. 27, 721-729.
9. Freist, W., Vehrey, J.F., Ruhlmann, A., Gauss, D.H. & Arnez, J.G. (1999) Histidyl-tRNA synthetase. Biol. Chem. 380, 623-646.
10. Yarus, M. (2000) Perspectives: protein synthesis. Unraveling the riddle of ProCys tRNA synthetase. Science 287, 440-441.
11. Stathopoulos, C., Li, T., Longman, R., Vethknecht, V.C., Becker, H.D., Ibba, M. & Soell, D. (2000) One polypeptide with two aminoacyl-tRNA synthetase activities. Science 287, 479-482.
12. Martinis, S.A., Plateau, P., Cavarelli, J. & Florentz, C. (1999) Aminoacyl-tRNA synthetases: A family of expanding functions. EMBO J. 18, 4591-4596.
13. Sissler, M., Delorme, C., Bond, J., Ehrlich, D., Renault, P. & Franclyn, C. (1999) An aminoacyl-tRNA synthetase paralog with a catalytic core in histidine biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 96, 8995-8990.
14. Fan, L., Sanschagrin, P.C., Kaguni, L.S. & Kuhn, L. (1999) The accessory subunit of mtDNA polymerase shares structural homology with aminoacyl-tRNA synthetases: Implications for a dual role as a primer recognition factor and processivity clamp. Proc. Natl. Acad. Sci. U.S.A. 96, 9527-9532.
15. Fersht, A.R. (1977) Enzyme Structure and Mechanism, 263 pp., Freeman, San Francisco.
16. Giege, R., Frugier, M. & Rudinger, J. (1998) tRNA mimics. Curr. Opin. Struc. Biol. 8, 286-293.
17. Goldgur, Y., Mosyak, L., Reshetnikova, L., Ankilova, V., Lavrik, O., Khodyreva, S. & Safro, M. (1997) The crystal structure of phenylalanyl-tRNA synthetase from Thermus thermophilus complexed with cognate tRNA Phe. Structure 5, 59-68.
18. Bullard, J.M., Cai, Y.-C, Demeler, B. & Spremuli, L.L. (1999) Expression and characterization of human mitochondrial phenylalanyl-tRNA synthetase. J. Mol. Biol. 288, 567-577.
19. Cussack, S. (1995) Eleven down and nine to go. Nature Struct. Biol. 2, 824-831.
21. Arnez, J.G. & Moras, D. (1997) Structural and functional consideration of the aminoacylation reaction. Trends Biochem. Sci. 22, 211- 216.
22. Schimmel, P. & Wang, C.-C. (1999) Species barrier to RNA recognition overcome with nonspecific RNA binding domains. J. Biol. Chem. 274, 16508-16512.
23. Morales, A.J., Swairjo, M.A. & Schimmel, P. (1999) Structure specific tRNA-binding protein from the extreme thermophile Aquifex aeolicus. EMBO J. 18, 3475-3483.
25. Wolf, Y.I., Aravind, L., Grishin, N.V. & Koonin, E.V. (1999) Evolution of aminoacyl-tRNA synthetases analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. Genome Res. 9, 689-710.
26. Doolittle, F. & Handy, J. (1998) Evolutionary anomalies among the aminoacyl-tRNA synthetases. Curr. Opin. Gen. Develop. 8, 630-636.
27. Tumbula, D., Vothknecht, U.C., Kim, H.-S., Ibba, M., Min, B., Li, T., Pelaschier, J., Stathopoulos, C., Becker, H. & Soell, D. (1999) Archaeal aminoacyl-tRNA synthesis: Diverse replaces dogma. Genetics 152, 1269-1276.
28. Ibba, M., Losey, H.C., Kawarabayashi, Y., Kikuchi, Y., Bunjun, S. & Soell, D. (1999) Substrate recognition by class I lysyl-tRNA synthetases: A molecular basis for gene displacement. Proc. Natl. Acad. Sci. U.S.A. 96, 418- 423.
29. Schimmel, P. & Ribas de Pouplana, L. (1999) Genetic code origins: Experiments confirm phylogenetic predictions and may explain a puzzle. Proc. Natl. Acad. Sci. U.S.A. 96, 327- 328.
30. Nureki, O., Vassylyev, D.G., Tateno, M., Shimada, A., Nakama, T., Fukai, S., Konno, M., Hendrickson, T.L., Schimmel, P. & Yokoyama, S. (1998) Enzyme structure with two catalytic sites for double-sieve selection of substrate. Science 280, 578-582.
31. Silvian, L.F., Wang, J. & Steitz, T.A. (1999) Insight into editing from an Ile-tRNA synthetase structure with tRNA-Ile and mupirocin. Science 285, 1074-1077.
32. Jakubowski, H. (1998) tRNA synthetase proofreading of amino acids; in Encyclopedia of Life Science, Mcmillan Reference Ltd., London (in press).
33. Jakubowski, H. (1999) Misacylation of tRNALys with noncognate amino acids by lysyl-tRNA synthetase. Biochemistry 38, 8088-8093.
34. Zamecnik, P.C., Stephenson, M.L., Janeway, C.M. & Randerath, K. (1966) Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-tRNA synthetase. Biochem. Biophys. Res. Commun. 24, 91-97.
35. Jakubowski, H. (1983) Synthesis of diadenosine 5',5'"-P1, P4-tetraphosphate and related compounds by plant (Lupinus luteus) seryl-tRNA and phenylalanyl-tRNA synthetases. Acta Biochim. Polon. 30, 51-69.
37. Nishimura, A. (1998) The timing of cell division: Ap4A as a signal. Trends Biochem. Sci. 23, 157-159.
38. Kisselev, L.L., Justesen, J., Wolfson, A.D. & Frolova, L.Y. (1998) Diadenosine oligophosphates (ApnA), a novel class of signaling molecules. FEBSLett. 427, 157-163.
39. Caprara, M.G., Lehnert, V., Lambowitz, A.M. & Westhof, E. (1996) A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structure motif in the group I intron catalytic core. Cell 87, 1135-1145.
40. Sankaranarayanan, R., Dock-Bregon, A.-C., Romby, P., Caillet, J., Springer, M., Rees, B., Ehresmann, C., Ehresmann, B. & Moras, D. (1999) The structure of threonyl-tRNA synthetase-tRNAThr complex enlightens its repressor activity and reveals an essential zinc ion in the active site. Cell 97, 371-381.
41. Stoldt, M., Wohnert, J., Gorlach, M. & Brown, L.R. (1998) The NMR structure of Escherichia coli ribosomal protein L25 shows homology to general stress proteins and glutaminyl-tRNA synthetases. EMBO J. 17, 6377-6384.
42. Lamour, V., Quevillon, S., Diriong, S., N'Guyen, V.C., Lipinski, M. & Mirande, M. (1994) Evolution of the Glx-tRNA synthetase family: The glutaminyl enzyme as a case of horizontal gene transfer. Proc. Natl. Acad. Sci. U.S.A. 91, 8670-8674.
43. Brown, J.R. & Doolittle, W.F. (1999) Gene descent, duplication and horizontal transfer in the evolution of glutamyl- and glutaminyl- tRNA synthetases. J. Mol. Evol. 49, 485-495.
44. Norcum, M.T. & Warrington, R.A. (1998) Structural analysis of the multiple aminoacyl-tRNA synthetase complex: A three domain model based on reversible chemical crosslinking. Protein Sci. 7, 79-87.
45. Quevillon, S., Agou, F., Robinson, J.-C. & Mirande, M. (1997) The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine. J. Biol. Chem.. 272, 32573-32579.
46. Kao, J., Ryan, J., Brett, G., Chen, J., Shen, H., Fan, Y.-G., Godman, G., Familletti, P.C., Wang, F., Pan, Y.-C.E., Stern, D. & Clauss, M. (1992) Endothelial monocyte-activating polypeptide II. J. Biol. Chem. 267, 20239-20247.
47. Deniziak, M., Mirande, M. & Barciszewski, J. (1998) Cloning and sequencing of cDNA encoding the rice methionyl-tRNA synthetase. Acta Biochim. Polon. 45, 669-676.
48. Park, S.G., Jung, K.H., Lee, J.S., Jo, Y.J., Motegi, H., Kim, S. & Shiba, K. (1999) Precursor of pro-apoptotic cytokine modulated aminoacylation activity of tRNA synthetase. J. Biol. Chem. 274, 16673-16676.
49. Simos, G., Segref, A., Fasiolo, F., Hellmuth, K., Shevchenko, A., Mann, M. & Hurt, E.C. (1996) The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases. EMBO J. 15, 5437-5448.
50. Simos, G., Sauer, A., Fasiolo, F. & Hurt, E.C. (1998) A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases. Mol. Cell 1, 235-242.
51. Frantz, J.D. & Gilbert, W. (1995) A novel yeast gene product, G4p1, with a specific affinity for quadruplex nucleic acids. J. Biol. Chem. 270, 20692-20697.
52. Wakasugi, K. & Schimmel, P. (1999) Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science 284, 147-151.
53. Weiner, A.M. & Maizels, N. (1999) A deadly double life. Science284, 63-64.
54. Quevillon, S., Robinson, J.-C., Berthonneau, E., Siatecka, M. & Mirande, M. (1999) Macromolecular assemblage of aminoacyl-tRNA synthetases: Identification of protein-protein interactions and characterization of a core protein. J. Mol. Biol. 285, 183-195.
55. Norcum, M.T. (1999) Ultrastructure of the eukaryotic aminoacyl-tRNA synthetase complex derived from two dimensional averaging and classification of negatively stained electron microscopic images. FEBS Lett. 447, 217-222.
56. Lund, E. & Dahlberg, J. (1998) Proofreading and aminoacylation of tRNA before export from nucleus. Science 282, 2082-2085.
58. Schimmel, P. & Wang, C.-C. (1999) Getting tRNA synthetases into nucleus, Trends Biochem. Sci. 24, 127-128.
59. Strasser, K. & Hurt, E. (1999) Nuclear RNA export in yeast. FEBS Lett. 452, 77-81.
60. Uwer, U., Willmitzer, L. & Altmann, T. (1998) Inactivation of a glycyl-tRNA synthetase leads to an arrest in plant embryo development. Plant Cell 10, 1277-1294.
61. Cline, T.W. & Meyer, B.J. (1996) Vive la difference: Males vs females in flies vs worms. Annu. Rev. Genet. 30, 637-702.
62. Stizinger, S.M., Pellicena-Palle, A., Albrecht, E.B., Gajewski, K.M., Beckingham, K.M. & Saltz, H.K. (1999) Mutations in the predicted aspartyl-tRNA synthetase of Drosophila are lethal and function as dosage-sensitive maternal modifiers of the sex determination gene Sex-lethal. Mol. Gen. Genet. 261, 142-151.
63. Seshaiah, P. & Andrew, D.J. (1999) WRS-85D: A tryptophanyl-tRNA synthetase expressed to high levels in the developing Drosophila salivary gland. Mol. Biol. Cell 10, 1595-1608.
65. Beaulande, M., Tarbouriech, N. & Hartlen, M. (1999) Human cytosolic asparaginyl-tRNA synthetase: cDNA sequence, functional expression in Escherichia coli and characterization as a human autoantigen. Nucleic Acids Res. 26, 521-524.
66. Kunst, C.B., Mezey, E., Brownstein, M.J. & Patterson, D. (1997) Mutations in the SOD1 associated with amyotrophic lateral sclerosis cause novel protein interaction. Nature Genet. 15, 91-94.
67. Schimmel, P., Tao, J. & Hill, J. (1998) Aminoacyl-tRNA synthetases as targets for new anti-infectives. FASEB J. 12, 1599-1609.
68. Moras, D. (1992) Structural and functional relationships between aminoacyl-tRNA synthetases. Trends Biochem. Sci. 17, 159-164.
69. Cusack, S. (1993) Sequence, structure and evolutionary relationships between class II aminoacyl-tRNA synthetases: An update. Biochimie 75, 1077-1081.
70. Carter, C.W., Jr. (1993) Cognition, mechanism and evolutionary relationships in aminoacyl-tRNA synthetases. Annu. Rev. Biochem. 62, 715-748.
71. Martinis, S.A. & Schimmel, P. (1996) Aminoacyl-tRNA synthetases: General features and relationships; in: Escherichia coli and Salmonella (Neidhardt, F.C., Jr., ed.) pp. 887-901, ASM Press, Washington, D.C.
72. Grunenberg, R.N. (1997) Anti-gram-positive agents. What we have and what we would like. Drugs 54 (Suppl. 6), 29-38.
73. Hiramatsu, K., Hanaki, H., Ino, T., Yabuta, K., Oguri, T. & Trenover, F.C. (1997) Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemotherap. 40, 135-136.
74. Fuller, A.T., Mellows, G., Woolford, M., Banks, G.T., Barrow, K.D. & Chain, E.B. (1971) Pseudomonic acid: An antibiotic produced by Pseudomonas fluorescens. Nature 234, 416-417.
75. Hughes, J. & Mellows, G. (1980) Interaction of pseudomonic acid A with Escherichia coliB isoleucyl-tRNA synthetase. Biochem. J. 191, 209-219.
76. Lechrer, A. & Kreutzer, R. (1998) The phenylalanyl-tRNA synthetase specifically binds DNA. J. Mol. Biol. 278, 897-901.
77. Goodwin, J.B. & Dreher, T.W. (1998) Transfer RNA mimicry in a new group of positive- strand RNA plant viruses, the furoviruses: Differential aminoacylation between the RNA components of one genome. Virology 246, 170-178.
78. Himeno, H., Sato, M., Tadaki, T., Fukushima, M., Ushida, C. & Muto, A. (1997) In vitro trans translation mediated by alanine-charged 10Sa RNA. J. Mol. Biol. 268, 803-808.
79. Felden, B., Hanawa, K., Atkins, J.F., Himeno, H., Muto, A., Gesteland, R.F., McCloskey, J.A. & Crain, P.F. (1998) Presence and location of modified nucleotides in Escherichia coli tmRNA: Structural mimicry with tRNA acceptor branches. EMBO J. 17, 3188-3196.