20 4 2008 8 Chinese Bulletin of Life Sciences Vol. 20, No. 4 Aug., 2008 1004-0374(2008)04-0667-06 -trna 200031 -trna (aars) trna aars aars aars -trna Q523; Q783.1; R915 A Physiology, pathology and drug design related with editing of aminoacyl-trna synthetase YAO Peng, WANG En-duo* (State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China) Abstract: Aminoacyl-tRNA synthetases (aarss) catalyse aminoacylation of their cognate trnas for protein biosynthesis. Many aarss developed editing function under the stress of evolutionary selection for translation fidelity. Recently the investigators pay more attention to the relation between the editing function and human health. Here, a few impressive progresses in understanding the cell physiology, pathology and drug design related with editing function of aminoacyl-trna synthetase were reviewed. Key words: aminoacyl-trna synthetase; editing; physiology; pathology; drug design [1] Leu/ Ser [2,3] -trna (aminoacyl-trna synthetase, aars) trna -trna [4,5] 20 aars 10 aars [6] aars 2008-01-03 2008-03-28 (2006CB 910301) (06JC14076) * E-mail: edwang@sibs.ac.cn
668 aars a - - -trna (LeuRS IleRS ValRS) [7-9] - - - -trna (ThrRS ProRS AlaRS PheRS) [10-13] aars CP1 [14] aars [11,15-17] 2006 Lee [18] AlaRS (A734E) (cerebellar Purkinje cell) aars aars aars 1 IleRS 1.1 Pezo [19] DNA (Escherichia coli) IleRS iles Ala iles 10 (T241 N250) IleRS Ala Val-tRNA Ile trna ATP [19] (Ile) (Nva) IleRS iles Ala AlaXp AlaXp iles Ala AlaXp 203 Ile Nva IleRS [19] Ile Val Leu ( ilvge) PS7068 ilesala β1412 Ile Leu Val Ile Leu Val Nva PS7068 β1412 β1412 trna Ile Nva 10 h 15 h β1412 PS7068 Nva Ile [19] IleRS ( Nva) trna iles Ala IleRS ( Nva) ( Ile) 1.2 IleRS Bacher [20] iles Ala IleRS iles Ala [20] Nva iles Ala Nva IleRS iles Ala [20] aars IleRS Bacher [20]
-trna 669 IleRS iles Ala A DNA DNA IleRS DNA IleRS iles Ala DNA IleRS iles Ala DNA (N-methyl-N'-nitro-N-nitrosoguanidine 2- aminopurine) 1.3 IleRS SOS Bacher [21] iles Ala IleRS IleRS DNA DNA SOS aars DNA [22] aars 2 ValRS(mcValRS) Nangle [23] mcvalrs T535P mcvalrs mcvalrs-t535p Nangle [23] (MFP) mcvalrs mcvalrs- T535P NIH/3T3 N- 295 EF1H -trna Nangle [23] mcvalrs-t535p MFP - 24 48 h mcvalrs Val α- ( ) mcvalrs-t535p 100 µmol/l α- 2 mmol/l α- mcvalrs- T535P mcvalrs-t535p Caspase-3 [23] Nangle [23] Thr Val (EGFP) T65V 12 18 h mcvalrs mcvalrs-t535p EGFP EGFP-T65V 65 Val Thr EGFP [23] aars [12,24] (Candida albicans)
670 1 aars [23] 50% [2,3] mcvalrs ( 1) 3 LeuRS aars aars (1) aars aars aars aars aars (2) 20 aars 20 aars (3) aars (4) aars (5) aars aars aars aars A mupirocin [25] mupirocin IleRS IleRS IleRS IleRS 8 000 aars 2007 Anacor LeuRS 5- fluoro- 1,3-dihydro- 1-hydroxy- 2,1-benzoxaborole (AN2690) 2 ( ) [26] LeuRS AN2690 trna 3' 2' 2 AN2690
-trna 671 3' trna Leu LeuRS trna Leu trna Leu 3' trna Leu AN2690 AN2690 AN2690 aars aars 4 aars aars aars aars aars aars aars aars 2000 -trna (LeuRS) Aquifex aeolicus Escherichia coli (Giardia lamblia) (Saccharomyces cerevisiae) LeuRS [9,27,28] LeuRS aars aars [1] Schimmel P, Ribas de Pouplana L. Formation of two classes of trna synthetases in relation to editing functions and genetic code. Cold Spring Harb Symp Quant Biol, 2001, 66: 161-6 [2] Santos MA, Cheesman C, Costa V, et al. Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp. Mol Microbiol, 1999, 31(3): 937-47 [3] Santos MA, Ueda T, Watanabe K, et al. The non-standard genetic code of Candida spp.: an evolving genetic code or a novel mechanism for adaptation? Mol Microbiol, 1997, 26 (3): 423-31 [4] Schimmel P. Aminoacyl-tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem, 1987, 56: 125-58 [5] Ibba M, Söll D. Aminoacyl-tRNA synthesis. Annu Rev Biochem, 2000, 69: 617-50 [6] Eriani G, Delarue M, Poch O, et al. Partition of trna synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature, 1990, 347(6289): 203-6 [7] Eldred EW, Schimmel P. Rapid deacylation by isoleucyl transfer ribonucleic acid synthetase of isoleucine-specific transfer ribonucleic acid aminoacylated with valine. J Biol Chem, 1972, 247(9): 2961-4 [8] Fersht A, Kaethner M. Enzyme hyperspecificity. Rejection of threonine by the valyl-trna synthetase by misacylation and hydrolytic editing. Biochemistry, 1976, 15(15): 3342-6 [9] Chen JF, Guo NN, Li T, et al. CP1 domain in Escherichia coli leucyl-trna synthetase is crucial for its editing function. Biochemistry, 2000, 39(22): 6726-31 [10] Beuning PJ, Musier-Forsyth K. Hydrolytic editing by a class II aminoacyl-trna synthetase. Proc Natl Acad Sci USA, 2000, 97(16): 8916-20 [11] Dock-Bregeon A, Sankaranarayanan R, Romby P, et al. Transfer RNA-mediated editing in threonyl-trna synthetase. The class II solution to the double discrimination problem. Cell, 2000, 103(6): 877-84 [12] Beebe K, Ribas de Pouplana L, Schimmel P. Elucidation of trna-dependent editing by a class II trna synthetase and significance for cell viability. EMBO J, 2003, 22(3): 668-75 [13] Roy H, Ling J, Irnov M, et al. Post-transfer editing in vitro and in vivo by the subunit of phenylalanyl-trna synthetase. EMBO J, 2005, 23(23): 4639-48 [14] Nureki O, Vassylyev D, Tateno M, et al. Enzyme structure with two catalytic sites for double-sieve selection of substrate. Science, 1998, 280(5363): 578-82 [15] Wong F, Beuning P, Silvers C, et al. An isolated class II aminoacyl-trna synthetase insertion domain is functional in amino acid editing. J Biol Chem, 2003, 278(52): 52857-64 [16] Kotik-Kogan O, Moor N, Tworowski D, et al. Structural basis for discrimination of L-phenylalanine from L-tyrosine by phenylalanyl-trna synthetase. Structure, 2005, 13(12): 1799-807 [17] Ishijima J, Uchida Y, Kuroishi C, et al. Crystal structure of alanyl-trna synthetase editing-domain homolog (PH0574) from a hyperthermophile, Pyrococcus horikoshii OT3 at 1. 45 Å resolution. Proteins, 2006, 62(4): 1133-7 [18] Lee J W, Beebe K, Nangle L A, et al. Editing-defective trna
672 synthetase causes protein misfolding and neurodegeneration. Nature, 2006, 443(7107): 50-5 [19] Pezo V, Metzgar D, Hendrickson TL, et al. Artificially ambiguous genetic code confers growth yield advantage. Proc Natl Acad Sci USA, 2004, 101(23): 8593-7 [20] Bacher JM, de Crecy-Lagard V, Schimmel PR. Inhibited cell growth and protein functional changes from an editing-defective trna synthetase. Proc Natl Acad Sci USA, 2005, 102(5): 1697-701 [21] Bacher JM, Schimmel P. An editing-defective aminoacyltrna synthetase is mutagenic in aging bacteria via the SOS response. Proc Natl Acad Sci USA, 2007, 104(6): 1907-12 [22] Goodman MF. Error-prone repair DNA polymerases in prokaryotes and eukaryotes. Annu Rev Biochem, 2002, 71: 17-50 [23] Nangle LA, Motta CM, Schimmel P. Global effects of mistranslation from an editing defect in mammalian cells. Chem Biol, 2006, 13(10): 1091-100 [24] Nangle LA, de Crecy Lagard V, Doring V, et al. Genetic code ambiguity. Cell viability related to the severity of editing defects in mutant trna synthetases. J Biol Chem, 2002, 277(48): 45729-33 [25] Silvian LF, Wang J, Steitz TA. Insights into editing from an ile-trna synthetase structure with trnaile and mupirocin. Science, 1999, 285(5430): 1074-7 [26] Rock F L, Mao W, Yaremchuk A, et al. An antifungal agent inhibits an aminoacyl-trna synthetase by trapping trna in the editing site. Science, 2007, 316(5832): 1759-61 [27] Zhao MW, Zhu B, Hao R, et al. Leucyl-tRNA synthetase from the ancestral bacterium Aquifex aeolicus contains relics of synthetase evolution. EMBO J, 2005, 24(7): 1430-9 [28] Ling C, Yao YN, Zheng YG, et al. The C-terminal appended domain of human cytosolic leucyl-trna synthetase is indispensable in its interaction with arginyl-trna synthetase in the multi-trna synthetase complex. J Biol Chem, 2005, 280(41): 34755-63 Chinese Bulletin of Life Sciences Chinese Bulletin of Life Sciences (Bimonthly) ( )(1988 ) (Started in 1988) 2008 8 20 4 ( 121 ) Aug., 2008 Vol.20 No.4 2 ( 319 200031) cbls@sibs.ac.cn ( 320 200031) ( 782 ) 3101044000449 2008 by Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Edited by GUAN Xing-hua, YUE Dong-fang, YU Jian-rong Editorial Office of Chinese Bulletin of Life Sciences (319 Yueyang Road, Shanghai 200031, China) Editor-in-Chief LIN Qi-shui Sponsored by Department of Life Sciences, National Natural Science Foundation of China; Bureau of Life Sciences and Biotechnology, Chinese Academy of Sciences; Division of Life Sciences and Medicine, Chinese Academy of Sciences; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Published by Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Distributed by Shanghai Post Office Subscripted by Local Post Offices Overseas Distributed by China National Publishing Industry Trading Corporation (P.O.Box 782, Beijing, China) Cable: CNPITC ISSN 1004-0374 CN 31-1600/Q : 4-628 : DK 31002 : 25.00