Aminoacyl-tRNA synthetase - a molecular multitasker.
aminoacyl tRNA synthetase
catalytic activity
infectious/non-infectious diseases
noncanonical functions
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
31
08
2023
received:
05
12
2022
accepted:
12
09
2023
medline:
30
10
2023
pubmed:
1
10
2023
entrez:
30
9
2023
Statut:
ppublish
Résumé
Aminoacyl-tRNA synthetases (AaRSs) are valuable "housekeeping" enzymes that ensure the accurate transmission of genetic information in living cells, where they aminoacylated tRNA molecules with their cognate amino acid and provide substrates for protein biosynthesis. In addition to their translational or canonical function, they contribute to nontranslational/moonlighting functions, which are mediated by the presence of other domains on the proteins. This was supported by several reports which claim that AaRS has a significant role in gene transcription, apoptosis, translation, and RNA splicing regulation. Noncanonical/ nontranslational functions of AaRSs also include their roles in regulating angiogenesis, inflammation, cancer, and other major physio-pathological processes. Multiple AaRSs are also associated with a broad range of physiological and pathological processes; a few even serve as cytokines. Therefore, the multifunctional nature of AaRSs suggests their potential as viable therapeutic targets as well. Here, our discussion will encompass a range of noncanonical functions attributed to Aminoacyl-tRNA Synthetases (AaRSs), highlighting their links with a diverse array of human diseases.
Identifiants
pubmed: 37776328
doi: 10.1096/fj.202202024RR
doi:
Substances chimiques
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23219Informations de copyright
© 2023 Federation of American Societies for Experimental Biology.
Références
Steiner RE, Ibba M. Regulation of tRNA-dependent translational quality control. IUBMB Life. 2019;71:1150-1157. doi:10.1002/iub.2080
Rosenberger RF, Foskett G. An estimate of the frequency of in vivo transcriptional errors at a nonsense codon in Escherichia coli. Mol Gen Genet. 1981;183:561-563. doi:10.1007/bf00268784
Kunkel TA, Bebenek K. DNA replication fidelity. Annu Rev Biochem. 2000;69:497-529. doi:10.1146/annurev.biochem.69.1.497
Bouadloun F, Donner D, Kurland CG. Codon-specific missense errors in vivo. EMBO J. 1983;2:1351-1356.
Pang L, Weeks SD, Van Aerschot A. Aminoacyl-tRNA synthetases as valuable targets for antimicrobial drug discovery. Int J Mol Sci. 2021;22. doi:10.3390/ijms22041750
Gill J, Sharma A. Exploration of aminoacyl-tRNA synthetases from eukaryotic parasites for drug development. J Biol Chem. 2023;299:102860.
Wei N, Zhang Q, Yang XL. Neurodegenerative Charcot-Marie-tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases. J Biol Chem. 2019;294:5321-5339. doi:10.1074/jbc.REV118.002955
Nagao A, Suzuki T, Katoh T, Sakaguchi Y, Suzuki T. Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. Proc Natl Acad Sci USA. 2009;106:16209-16214. doi:10.1073/pnas.0907602106
Rubio Gomez MA, Ibba M. Aminoacyl-tRNA synthetases. RNA. 2020;26:910-936. doi:10.1261/rna.071720.119
Kwon NH, Fox PL, Kim S. Aminoacyl-tRNA synthetases as therapeutic targets. Nat Rev Drug Discov. 2019;18:629-650. doi:10.1038/s41573-019-0026-3
Newberry KJ, Hou Y-M, Perona JJ. Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase. EMBO J. 2002;21:2778-2787.
Ling J, Peterson KM, Simonović I, Cho C, Söll D, Simonović M. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment. Proc Natl Acad Sci USA. 2012;109:3281-3286.
Sprinzl M. Elongation factor Tu: a regulatory GTPase with an integrated effector. Trends Biochem Sci. 1994;19:245-250.
Harvey KL, Jarocki VM, Charles IG, Djordjevic SP. The diverse functional roles of elongation factor Tu (EF-Tu) in microbial pathogenesis. Front Microbiol. 2019;10:2351.
Jones TE, Alexander RW, Pan T. Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase. Proc Natl Acad Sci. 2011;108:6933-6938.
Moras D. Proofreading in translation: dynamics of the double-sieve model. Proc Natl Acad Sci. 2010;107:21949-21950.
Jani J, Pappachan A. A review on quality control agents of protein translation-the role of trans-editing proteins. Int J Biol Macromol. 2022;199:252-263. doi:10.1016/j.ijbiomac.2021.12.176
Routh SB, Pawar KI, Ahmad S, et al. Elongation factor Tu prevents misediting of Gly-tRNA (Gly) caused by the design behind the chiral proofreading site of D-aminoacyl-tRNA deacylase. PLoS Biol. 2016;14:e1002465.
Ling J, So BR, Yadavalli SS, et al. Resampling and editing of mischarged tRNA prior to translation elongation. Mol Cell. 2009;33:654-660.
Ribas de Pouplana L, Schimmel P. Aminoacyl-tRNA synthetases: potential markers of genetic code development. Trends Biochem Sci. 2001;26:591-596. doi:10.1016/s0968-0004(01)01932-6
Perona JJ, Gruic-Sovulj I. Synthetic and editing mechanisms of aminoacyl-tRNA synthetases. Top Curr Chem. 2014;344:1-41. doi:10.1007/128_2013_456
Eriani G, Delarue M, Poch O, Gangloff J, Moras D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990;347:203-206. doi:10.1038/347203a0
Bullwinkle TJ, Ibba M. Emergence and evolution. Top Curr Chem. 2014;344:43-87. doi:10.1007/128_2013_423
Yao P, Poruri K, Martinis SA, Fox PL. Non-catalytic regulation of gene expression by aminoacyl-tRNA synthetases. Top Curr Chem. 2014;344:167-187. doi:10.1007/128_2013_422
Guo M, Yang XL, Schimmel P. New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol. 2010;11:668-674. doi:10.1038/nrm2956
Yao P, Fox PL. Aminoacyl-tRNA synthetases in cell signaling. Enzyme. 2020;48:243-275. doi:10.1016/bs.enz.2020.04.002
Guo M, Schimmel P, Yang X-L. Functional expansion of human tRNA synthetases achieved by structural inventions. FEBS Lett. 2010;584:434-442.
Yao P, Fox PL. Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med. 2013;5:332-343. doi:10.1002/emmm.201100626
Park SG, Schimmel P, Kim S. Aminoacyl tRNA synthetases and their connections to disease. Proc Natl Acad Sci U S A. 2008;105:11043-11049. doi:10.1073/pnas.0802862105
Wahab SZ, Yang DC. Synthesis of diadenosine 5′,5‴ -P1,P4-tetraphosphate by lysyl-tRNA synthetase and a multienzyme complex of aminoacyl-tRNA synthetases from rat liver. J Biol Chem. 1985;260:5286-5289.
Arif A, Jia J, Moodt RA, DiCorleto PE, Fox PL. Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control. Proc Natl Acad Sci USA. 2011;108:1415-1420. doi:10.1073/pnas.1011275108
Hoffman RM. Tumor-seeking salmonella amino acid auxotrophs. Curr Opin Biotechnol. 2011;22:917-923. doi:10.1016/j.copbio.2011.03.009
Park BJ, Kang JW, Lee SW, et al. The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell. 2005;120:209-221. doi:10.1016/j.cell.2004.11.054
Wakasugi K, Slike BM, Hood J, et al. A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci USA. 2002;99:173-177. doi:10.1073/pnas.012602099
Arif A, Yao P, Terenzi F, Jia J, Ray PS, Fox PL. The GAIT translational control system. Wiley Interdiscip Rev RNA. 2018;9:e1441.
Han JM, Jeong SJ, Park MC, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149:410-424. doi:10.1016/j.cell.2012.02.044
Hahn H, Park SH, Kim HJ, Kim S, Han BW. The DRS-AIMP2-EPRS subcomplex acts as a pivot in the multi-tRNA synthetase complex. IUCrJ. 2019;6:958-967. doi:10.1107/s2052252519010790
Park SG, Choi EC, Kim S. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis. IUBMB Life. 2010;62:296-302. doi:10.1002/iub.324
Park SG, Kang YS, Ahn YH, et al. Dose-dependent biphasic activity of tRNA synthetase-associating factor, p43, in angiogenesis. J Biol Chem. 2002;277:45243-45248. doi:10.1074/jbc.M207934200
Choi JW, Um JY, Kundu JK, Surh YJ, Kim S. Multidirectional tumor-suppressive activity of AIMP2/p38 and the enhanced susceptibility of AIMP2 heterozygous mice to carcinogenesis. Carcinogenesis. 2009;30:1638-1644. doi:10.1093/carcin/bgp170
Yu YC, Han JM, Kim S. Aminoacyl-tRNA synthetases and amino acid signaling. Biochim Biophys Acta Mol Cell Res. 2021;1868:118889. doi:10.1016/j.bbamcr.2020.118889
Choi JW, Kim DG, Lee AE, et al. Cancer-associated splicing variant of tumor suppressor AIMP2/p38: pathological implication in tumorigenesis. PLoS Genet. 2011;7:e1001351. doi:10.1371/journal.pgen.1001351
Park SG, Kang YS, Kim JY, et al. Hormonal activity of AIMP1/p43 for glucose homeostasis. Proc Natl Acad Sci U S A. 2006;103:14913-14918. doi:10.1073/pnas.0602045103
Jin M. Unique roles of tryptophanyl-tRNA synthetase in immune control and its therapeutic implications. Exp Mol Med. 2019;51:1-10. doi:10.1038/s12276-018-0196-9
Guo M, Yang XL. Architecture and metamorphosis. Top Curr Chem. 2014;344:89-118. doi:10.1007/128_2013_424
Cui H, Kapur M, Diedrich JK, Yates JR III, Ackerman SL, Schimmel P. Regulation of ex-translational activities is the primary function of the multi-tRNA synthetase complex. Nucleic Acids Res. 2021;49:3603-3616.
Negrutskii BS, Deutscher MP. Channeling of aminoacyl-tRNA for protein synthesis in vivo. Proc Natl Acad Sci USA. 1991;88:4991-4995.
Kerjan P, Cerini C, Sémériva M, Mirande M. The multienzyme complex containing nine aminoacyl-tRNA synthetases is ubiquitous from drosophila to mammals. Biochim Biophys Acta. 1994;1199:293-297. doi:10.1016/0304-4165(94)90009-4
Lee SW, Cho BH, Park SG, Kim S. Aminoacyl-tRNA synthetase complexes: beyond translation. J Cell Sci. 2004;117:3725-3734. doi:10.1242/jcs.01342
Kang T, Kwon NH, Lee JY, et al. AIMP3/p18 controls translational initiation by mediating the delivery of charged initiator tRNA to initiation complex. J Mol Biol. 2012;423:475-481. doi:10.1016/j.jmb.2012.07.020
Robinson JC, Kerjan P, Mirande M. Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J Mol Biol. 2000;304:983-994. doi:10.1006/jmbi.2000.4242
Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M. Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J Mol Biol. 1999;285:183-195. doi:10.1006/jmbi.1998.2316
Han JM, Lee MJ, Park SG, et al. Hierarchical network between the components of the multi-tRNA synthetase complex: implications for complex formation. J Biol Chem. 2006;281:38663-38667. doi:10.1074/jbc.M605211200
Zhou Z, Sun B, Huang S, Yu D, Zhang X. Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer. Cell Death Dis. 2020;11:579. doi:10.1038/s41419-020-02794-2
Cho HY, Lee HJ, Choi YS, et al. Symmetric assembly of a decameric subcomplex in human multi-tRNA synthetase complex via interactions between glutathione transferase-homology domains and aspartyl-tRNA synthetase. J Mol Biol. 2019;431:4475-4496.
Khan K, Baleanu-Gogonea C, Willard B, Gogonea V, Fox PL. 3-dimensional architecture of the human multi-tRNA synthetase complex. Nucleic Acids Res. 2020;48:8740-8754.
Dias J, Renault L, Pérez J, Mirande M. Small-angle X-ray solution scattering study of the multi-aminoacyl-tRNA synthetase complex reveals an elongated and multi-armed particle. J Biol Chem. 2013;288:23979-23989.
Lee SW, Kim G, Kim S. Aminoacyl-tRNA synthetase-interacting multi-functional protein 1/p43: an emerging therapeutic protein working at systems level. Expert Opin Drug Discov. 2008;3:945-957. doi:10.1517/17460441.3.8.945
Lee EY, Kim S, Kim MH. Aminoacyl-tRNA synthetases, therapeutic targets for infectious diseases. Biochem Pharmacol. 2018;154:424-434. doi:10.1016/j.bcp.2018.06.009
Ko Y-G, Park H, Kim T, et al. A cofactor of tRNA synthetase, p43, is secreted to up-regulate proinflammatory genes. J Biol Chem. 2001;276:23028-23033.
Park SG, Shin H, Shin YK, et al. The novel cytokine p43 stimulates dermal fibroblast proliferation and wound repair. Am J Pathol. 2005;166:387-398. doi:10.1016/s0002-9440(10)62262-6
Wang W, Tan J, Xing Y, et al. p43 induces IP-10 expression through the JAK-STAT signaling pathway in HMEC-1 cells. Int J Mol Med. 2016;38:1217-1224. doi:10.3892/ijmm.2016.2710
Kim JY, Kang YS, Lee JW, et al. p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance. Proc Natl Acad Sci USA. 2002;99:7912-7916. doi:10.1073/pnas.122110199
Kim MJ, Park BJ, Kang YS, et al. Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation. Nat Genet. 2003;34:330-336. doi:10.1038/ng1182
Choi JW, Lee JW, Kim JK, et al. Splicing variant of AIMP2 as an effective target against chemoresistant ovarian cancer. J Mol Cell Biol. 2012;4:164-173. doi:10.1093/jmcb/mjs018
Kwon NH, Kang T, Lee JY, et al. Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proc Natl Acad Sci U S A. 2011;108:19635-19640. doi:10.1073/pnas.1103922108
Kim KJ, Park MC, Choi SJ, et al. Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM. J Biol Chem. 2008;283:14032-14040. doi:10.1074/jbc.M800859200
Wu PC, Alexander HR, Huang J, et al. In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII). Cancer Res. 1999;59:205-212.
Shiba K. Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases. J Mol Evol. 2002;55:727-733. doi:10.1007/s00239-002-2368-3
Sajish M, Zhou Q, Kishi S, et al. Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling. Nat Chem Biol. 2012;8:547-554. doi:10.1038/nchembio.937
Ray PS, Sullivan JC, Jia J, Francis J, Finnerty JR, Fox PL. Evolution of function of a fused metazoan tRNA synthetase. Mol Biol Evol. 2011;28:437-447. doi:10.1093/molbev/msq246
Cerini C, Kerjan P, Astier M, Gratecos D, Mirande M, Sémériva M. A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. EMBO J. 1991;10:4267-4277.
Mukhopadhyay R, Jia J, Arif A, Ray PS, Fox PL. The GAIT system: a gatekeeper of inflammatory gene expression. Trends Biochem Sci. 2009;34:324-331. doi:10.1016/j.tibs.2009.03.004
Yao P, Potdar AA, Arif A, et al. Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression. Cell. 2012;149:88-100.
Bonfils G, Jaquenoud M, Bontron S, Ostrowicz C, Ungermann C, de Virgilio C. Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol Cell. 2012;46:105-110. doi:10.1016/j.molcel.2012.02.009
Xu X, Shi Y, Zhang HM, et al. Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat Commun. 2012;3:681. doi:10.1038/ncomms1686
Herzog W, Müller K, Huisken J, Stainier DY. Genetic evidence for a noncanonical function of seryl-tRNA synthetase in vascular development. Circ Res. 2009;104:1260-1266. doi:10.1161/circresaha.108.191718
Fukui H, Hanaoka R, Kawahara A. Noncanonical activity of seryl-tRNA synthetase is involved in vascular development. Circ Res. 2009;104:1253-1259. doi:10.1161/circresaha.108.191189
Ahn HC, Kim S, Lee BJ. Solution structure and p43 binding of the p38 leucine zipper motif: coiled-coil interactions mediate the association between p38 and p43. FEBS Lett. 2003;542:119-124. doi:10.1016/s0014-5793(03)00362-4
Zheng YG, Wei H, Ling C, Xu MG, Wang ED. Two forms of human cytoplasmic arginyl-tRNA synthetase produced from two translation initiations by a single mRNA. Biochemistry. 2006;45:1338-1344. doi:10.1021/bi051675n
Zhou X-L, Chen Y, Zeng QY, Ruan ZR, Fang P, Wang ED. Newly acquired N-terminal extension targets threonyl-tRNA synthetase-like protein into the multiple tRNA synthetase complex. Nucleic Acids Res. 2019;47:8662-8674.
Ryckelynck M, Giegé R, Frugier M. tRNAs and tRNA mimics as cornerstones of aminoacyl-tRNA synthetase regulations. Biochimie. 2005;87:835-845. doi:10.1016/j.biochi.2005.02.014
Putney SD, Schimmel P. An aminoacyl tRNA synthetase binds to a specific DNA sequence and regulates its gene transcription. Nature. 1981;291:632-635. doi:10.1038/291632a0
Springer M, Graffe M, Dondon J, Grunberg-Manago M. tRNA-like structures and gene regulation at the translational level: a case of molecular mimicry in Escherichia coli. EMBO J. 1989;8:2417-2424.
Springer M, Graffe M, Dondon J, et al. Translational control in E. coli: the case of threonyl-tRNA synthetase. Biosci Rep. 1988;8:619-632. doi:10.1007/BF01117341
Torres-Larios A, Dock-Bregeon AC, Romby P, et al. Structural basis of translational control by Escherichia coli threonyl tRNA synthetase. Nat Struct Biol. 2002;9:343-347. doi:10.1038/nsb789
Caillet J, Nogueira T, Masquida B, et al. The modular structure of Escherichia coli threonyl-tRNA synthetase as both an enzyme and a regulator of gene expression. Mol Microbiol. 2003;47:961-974. doi:10.1046/j.1365-2958.2003.03364.x
Jeong SJ, Park S, Nguyen LT, et al. A threonyl-tRNA synthetase-mediated translation initiation machinery. Nat Commun. 2019;10:1357. doi:10.1038/s41467-019-09086-0
Ryckelynck M, Masquida B, Giegé R, Frugier M. An intricate RNA structure with two tRNA-derived motifs directs complex formation between yeast aspartyl-tRNA synthetase and its mRNA. J Mol Biol. 2005;354:614-629. doi:10.1016/j.jmb.2005.09.063
Mohr G, Rennard R, Cherniack AD, Stryker J, Lambowitz AM. Function of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase in RNA splicing. Role of the idiosyncratic N-terminal extension and different modes of interaction with different group I introns. J Mol Biol. 2001;307:75-92. doi:10.1006/jmbi.2000.4460
Kittle JD Jr, Mohr G, Gianelos JA, Wang H, Lambowitz AM. The Neurospora mitochondrial tyrosyl-tRNA synthetase is sufficient for group I intron splicing in vitro and uses the carboxy-terminal tRNA-binding domain along with other regions. Genes Dev. 1991;5:1009-1021. doi:10.1101/gad.5.6.1009
Majumder AL, Akins RA, Wilkinson JG, Kelley RL, Snook AJ, Lambowitz AM. Involvement of tyrosyl-tRNA synthetase in splicing of group I introns in Neurospora crassa mitochondria: biochemical and immunochemical analyses of splicing activity. Mol Cell Biol. 1989;9:2089-2104. doi:10.1128/mcb.9.5.2089
Lamech LT, Saoji M, Paukstelis PJ, Lambowitz AM. Structural divergence of the group I intron binding surface in fungal mitochondrial Tyrosyl-tRNA synthetases that function in RNA splicing. J Biol Chem. 2016;291:11911-11927. doi:10.1074/jbc.M116.725390
Zamecnik P. Diadenosine 5′,5‴ -P1,P4-tetraphosphate (Ap4A): its role in cellular metabolism. Anal Biochem. 1983;134:1-10. doi:10.1016/0003-2697(83)90255-5
Bochner BR, Lee PC, Wilson SW, Cutler CW, Ames BN. AppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress. Cell. 1984;37:225-232. doi:10.1016/0092-8674(84)90318-0
Nie A, Sun B, Fu Z, Yu D. Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases. Cell Death Dis. 2019;10:901. doi:10.1038/s41419-019-2145-5
Lee YN, Nechushtan H, Figov N, Razin E. The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity. 2004;20:145-151. doi:10.1016/s1074-7613(04)00020-2
Yannay-Cohen N, Carmi-Levy I, Kay G, et al. LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell. 2009;34:603-611. doi:10.1016/j.molcel.2009.05.019
Ofir-Birin Y, Fang P, Bennett SP, et al. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol Cell. 2013;49:30-42. doi:10.1016/j.molcel.2012.10.010
Ruggiero RA, Bruzzo J, Chiarella P, Bustuoabad OD, Meiss RP, Pasqualini CD. Concomitant tumor resistance: the role of tyrosine isomers in the mechanisms of metastases control. Cancer Res. 2012;72:1043-1050. doi:10.1158/0008-5472.Can-11-2964
Hattori K, Naguro I, Runchel C, Ichijo H. The roles of ASK family proteins in stress responses and diseases. Cell Commun Signal. 2009;7:9. doi:10.1186/1478-811x-7-9
Ko YG, Kim EK, Kim T, et al. Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. J Biol Chem. 2001;276:6030-6036. doi:10.1074/jbc.M006189200
Vargas A, Rojas J, Aivasovsky I, et al. Progressive early-onset Leukodystrophy related to biallelic variants in the KARS gene: the first case described in Latin America. Genes (Basel). 2020;11:1519. doi:10.3390/genes11121437
Ognjenović J, Simonović M. Human aminoacyl-tRNA synthetases in diseases of the nervous system. RNA Biol. 2018;15:623-634. doi:10.1080/15476286.2017.1330245
Laurá M, Pipis M, Rossor AM, Reilly MM. Charcot-Marie-tooth disease and related disorders: an evolving landscape. Curr Opin Neurol. 2019;32:641-650. doi:10.1097/wco.0000000000000735
Antonellis A, Ellsworth RE, Sambuughin N, et al. Glycyl tRNA synthetase mutations in Charcot-Marie-tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet. 2003;72:1293-1299. doi:10.1086/375039
Jordanova A, Irobi J, Thomas FP, et al. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-tooth neuropathy. Nat Genet. 2006;38:197-202. doi:10.1038/ng1727
Latour P, Thauvin-Robinet C, Baudelet-Méry C, 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. doi:10.1016/j.ajhg.2009.12.005
Tsai PC, Soong BW, Mademan I, et al. A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Brain. 2017;140:1252-1266. doi:10.1093/brain/awx058
Morant L, Erfurth ML, Jordanova A. Drosophila models for Charcot-Marie-tooth neuropathy related to aminoacyl-tRNA synthetases. Genes (Basel). 2021;12:1437. doi:10.3390/genes12101519
Zhang H, Zhou ZW, Sun L. Aminoacyl-tRNA synthetases in Charcot-Marie-tooth disease: a gain or a loss? J Neurochem. 2021;157:351-369. doi:10.1111/jnc.15249
Nangle LA, Zhang W, Xie W, Yang XL, Schimmel P. Charcot-Marie-tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect. Proc Natl Acad Sci USA. 2007;104:11239-11244. doi:10.1073/pnas.0705055104
Safka Brozkova D, Deconinck T, Beth Griffin L, et al. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Brain. 2015;138:2161-2172. doi:10.1093/brain/awv158
McLaughlin HM, Sakaguchi R, Liu C, et al. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet. 2010;87:560-566. doi:10.1016/j.ajhg.2010.09.008
McLaughlin HM, Sakaguchi R, Giblin W, 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;33:244-253. doi:10.1002/humu.21635
Hyun YS, Park HJ, Heo SH, et al. Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-tooth neuropathy. Clin Genet. 2014;86:592-594. doi:10.1111/cge.12327
Storkebaum E, Leitão-Gonçalves R, Godenschwege T, et al. Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in drosophila features of human Charcot-Marie-tooth neuropathy. Proc Natl Acad Sci USA. 2009;106:11782-11787. doi:10.1073/pnas.0905339106
Niehues S, Bussmann J, Steffes G, et al. Impaired protein translation in drosophila models for Charcot-Marie-tooth neuropathy caused by mutant tRNA synthetases. Nat Commun. 2015;6:7520. doi:10.1038/ncomms8520
Antonellis A, Lee-Lin SQ, Wasterlain A, et al. Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. J Neurosci. 2006;26:10397-10406. doi:10.1523/jneurosci.1671-06.2006
Froelich CA, First EA. Dominant intermediate Charcot-Marie-tooth disorder is not due to a catalytic defect in tyrosyl-tRNA synthetase. Biochemistry. 2011;50:7132-7145. doi:10.1021/bi200989h
Seburn KL, Nangle LA, Cox GA, Schimmel P, Burgess RW. An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-tooth 2D mouse model. Neuron. 2006;51:715-726. doi:10.1016/j.neuron.2006.08.027
Achilli F, Bros-Facer V, Williams HP, et al. An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-tooth type 2D peripheral neuropathy. Dis Model Mech. 2009;2:359-373. doi:10.1242/dmm.002527
Lu J, Bergert M, Walther A, Suter B. Double-sieving-defective aminoacyl-tRNA synthetase causes protein mistranslation and affects cellular physiology and development. Nat Commun. 2014;5:5650. doi:10.1038/ncomms6650
Lee JW, Beebe K, Nangle LA, et al. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006;443:50-55. doi:10.1038/nature05096
Fu G, Xu T, Shi Y, Wei N, Yang XL. tRNA-controlled nuclear import of a human tRNA synthetase. J Biol Chem. 2012;287:9330-9334. doi:10.1074/jbc.C111.325902
Guo RT, Chong YE, Guo M, Yang XL. Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis. J Biol Chem. 2009;284:28968-28976. doi:10.1074/jbc.M109.030692
Howard OM, Dong HF, Yang D, et al. Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. J Exp Med. 2002;196:781-791. doi:10.1084/jem.20020186
Park MC, Kang T, Jin D, et al. Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis. Proc Natl Acad Sci USA. 2012;109:E640-E647. doi:10.1073/pnas.1200194109
Wakasugi K, Schimmel P. Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science. 1999;284:147-151. doi:10.1126/science.284.5411.147
Wakasugi K, Slike BM, Hood J, Ewalt KL, Cheresh DA, Schimmel P. Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase. J Biol Chem. 2002;277:20124-20126. doi:10.1074/jbc.C200126200
Turvey AK, Horvath GA, Cavalcanti ARO. Aminoacyl-tRNA synthetases in human health and disease. Front Physiol. 2022;13:1029218. doi:10.3389/fphys.2022.1029218
Scheper GC, van der Klok T, van Andel RJ, et al. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet. 2007;39:534-539. doi:10.1038/ng2013
van Berge L, Kevenaar J, Polder E, et al. Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways. Biochem J. 2013;450:345-350. doi:10.1042/bj20121564
Datt M, Sharma A. Evolutionary and structural annotation of disease-associated mutations in human aminoacyl-tRNA synthetases. BMC Genomics. 2014;15:1063. doi:10.1186/1471-2164-15-1063
Sarna JR, Hawkes R. Patterned Purkinje cell loss in the ataxic sticky mouse. Eur J Neurosci. 2011;34:79-86. doi:10.1111/j.1460-9568.2011.07725.x
Nangle LA, Motta CM, Schimmel P. Global effects of mistranslation from an editing defect in mammalian cells. Chem Biol. 2006;13:1091-1100. doi:10.1016/j.chembiol.2006.08.011
Williams AM, Martinis SA. Mutational unmasking of a tRNA-dependent pathway for preventing genetic code ambiguity. Proc Natl Acad Sci USA. 2006;103:3586-3591. doi:10.1073/pnas.0507362103
Casey JP, McGettigan P, Lynam-Lennon N, et al. Identification of a mutation in LARS as a novel cause of infantile hepatopathy. Mol Genet Metab. 2012;106:351-358. doi:10.1016/j.ymgme.2012.04.017
Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest. 2005;115:2679-2688. doi:10.1172/jci26390
Murrow L, Debnath J. Autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease. Annu Rev Pathol. 2013;8:105-137. doi:10.1146/annurev-pathol-020712-163918
Puffenberger EG, Jinks RN, Sougnez C, et al. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PloS One. 2012;7:e28936. doi:10.1371/journal.pone.0028936
Wolf NI, Salomons GS, Rodenburg RJ, et al. Mutations in RARS cause hypomyelination. Ann Neurol. 2014;76:134-139. doi:10.1002/ana.24167
Iqbal Z, Püttmann L, Musante L, et al. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration. Eur J Hum Genet. 2016;24:392-399. doi:10.1038/ejhg.2015.148
Nafisinia M, Sobreira N, Riley L, et al. Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease. Eur J Hum Genet. 2017;25:1134-1141. doi:10.1038/ejhg.2017.119
Mendes MI, Gutierrez Salazar M, Guerrero K, et al. Bi-allelic mutations in EPRS, encoding the Glutamyl-prolyl-aminoacyl-tRNA synthetase, cause a hypomyelinating leukodystrophy. Am J Hum Genet. 2018;102:676-684. doi:10.1016/j.ajhg.2018.02.011
Shukla A, das Bhowmik A, Hebbar M, et al. Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. J Hum Genet. 2018;63:19-25. doi:10.1038/s10038-017-0363-1
Coller HA, Grandori C, Tamayo P, et al. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci USA. 2000;97:3260-3265. doi:10.1073/pnas.97.7.3260
Sang Won L, Young Sun K, Sunghoon K. Multifunctional proteins in tumorigenesis: aminoacyl-tRNA Synthetases and translational components. Curr Proteomics. 2006;3:233-247. doi:10.2174/157016406780655577
Kushner JP, Boll D, Quagliana J, Dickman S. Elevated methionine-tRNA synthetase activity in human colon cancer. Proc Soc Exp Biol Med. 1976;153:273-276. doi:10.3181/00379727-153-39526
Forus A, Flørenes VA, Maelandsmo GM, Fodstad O, Myklebost O. The protooncogene CHOP/GADD153, involved in growth arrest and DNA damage response, is amplified in a subset of human sarcomas. Cancer Genet Cytogenet. 1994;78:165-171. doi:10.1016/0165-4608(94)90085-x
Nilbert M, Rydholm A, Mitelman F, Meltzer PS, Mandahl N. Characterization of the 12q13-15 amplicon in soft tissue tumors. Cancer Genet Cytogenet. 1995;83:32-36. doi:10.1016/s0165-4608(95)00016-x
Scandurro AB, Weldon CW, Figueroa YG, Alam J, Beckman BS. Gene microarray analysis reveals a novel hypoxia signal transduction pathway in human hepatocellular carcinoma cells. Int J Oncol. 2001;19:129-135. doi:10.3892/ijo.19.1.129
Wasenius VM, Hemmer S, Kettunen E, Knuutila S, Franssila K, Joensuu H. Hepatocyte growth factor receptor, matrix metalloproteinase-11, tissue inhibitor of metalloproteinase-1, and fibronectin are up-regulated in papillary thyroid carcinoma: a cDNA and tissue microarray study. Clin Cancer Res. 2003;9:68-75.
Nichols RC, Pai SI, Ge Q, Targoff IN, Plotz PH, 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;30:131-132. doi:10.1006/geno.1995.0028
Kjellman P, Lagercrantz S, Höög A, Wallin G, Larsson C, Zedenius J. Gain of 1q and loss of 9q21.3-q32 are associated with a less favorable prognosis in papillary thyroid carcinoma. Genes Chromosomes Cancer. 2001;32:43-49. doi:10.1002/gcc.1165
Park SG, Kim HJ, Min YH, et al. Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc Natl Acad Sci U S A. 2005;102:6356-6361. doi:10.1073/pnas.0500226102
Ichijo H, Nishida E, Irie K, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997;275:90-94. doi:10.1126/science.275.5296.90
Tobiume K, Matsuzawa A, Takahashi T, et al. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2001;2:222-228. doi:10.1093/embo-reports/kve046
Liu H, Lo CR, Czaja MJ. NF-kappaB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun. Hepatology. 2002;35:772-778. doi:10.1053/jhep.2002.32534
Baisch H. Elevated Ki-67 expression is correlated with TNFalpha- and IFNgamma-induced apoptosis in tumour cells. Cell Prolif. 2002;35:333-342. doi:10.1046/j.1365-2184.2002.00243.x
Miyaki M, Iijima T, Shiba K, et al. Alterations of repeated sequences in 5′ upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome. Oncogene. 2001;20:5215-5218. doi:10.1038/sj.onc.1204578
Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G. A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer. 1976;17:62-70. doi:10.1002/ijc.2910170110
Rodova M, Ankilova V, Safro MG. Human phenylalanyl-tRNA synthetase: cloning, characterization of the deduced amino acid sequences in terms of the structural domains and coordinately regulated expression of the alpha and beta subunits in chronic myeloid leukemia cells. Biochem Biophys Res Commun. 1999;255:765-773. doi:10.1006/bbrc.1999.0141
Kim DG, Choi JW, Lee JY, et al. Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration. FASEB J. 2012;26:4142-4159. doi:10.1096/fj.12-207639
Nam SH, Kim D, Lee MS, et al. Noncanonical roles of membranous lysyl-tRNA synthetase in transducing cell-substrate signaling for invasive dissemination of colon cancer spheroids in 3D collagen I gels. Oncotarget. 2015;6:21655-21674. doi:10.18632/oncotarget.4130
Kim SB, Kim HR, Park MC, et al. Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells. J Cell Biol. 2017;216:2201-2216. doi:10.1083/jcb.201605118
Oh AY, Jung YS, Kim J, et al. Inhibiting DX2-p14/ARF interaction exerts antitumor effects in lung cancer and delays tumor progression. Cancer Res. 2016;76:4791-4804. doi:10.1158/0008-5472.Can-15-1025
Ray PS, Fox PL. A post-transcriptional pathway represses monocyte VEGF-A expression and angiogenic activity. EMBO J. 2007;26:3360-3372. doi:10.1038/sj.emboj.7601774
Wang D, Zhao R, Qu YY, et al. Colonic lysine homocysteinylation induced by high-fat diet suppresses DNA damage repair. Cell Rep. 2018;25:398-412.e396. doi:10.1016/j.celrep.2018.09.022
Nam SH, Kim D, Lee D, et al. Lysyl-tRNA synthetase-expressing colon spheroids induce M2 macrophage polarization to promote metastasis. J Clin Invest. 2018;128:5034-5055. doi:10.1172/jci99806
Zhong L, Zhang Y, Yang JY, et al. Expression of IARS2 gene in colon cancer and effect of its knockdown on biological behavior of RKO cells. Int J Clin Exp Pathol. 2015;8:12151-12159.
Shin SH, Kim HS, Jung SH, Xu HD, Jeong YB, Chung YJ. Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis. Exp Mol Med. 2008;40:229-236. doi:10.3858/emm.2008.40.2.229
Zhou X, Xue L, Hao L, et al. Proteomics-based identification of tumor relevant proteins in lung adenocarcinoma. Biomed Pharmacother. 2013;67:621-627. doi:10.1016/j.biopha.2013.06.005
Di X, Jin X, Ma H, et al. The oncogene IARS2 promotes non-small cell lung cancer tumorigenesis by activating the AKT/MTOR pathway. Front Oncol. 2019;9:393. doi:10.3389/fonc.2019.00393
He Y, Gong J, Wang Y, et al. Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population. Mol Carcinog. 2015;54:577-583. doi:10.1002/mc.22128
Ireland L, Santos A, Campbell F, et al. Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer. Oncogene. 2018;37:2022-2036. doi:10.1038/s41388-017-0115-x
De Vincenzo A, Belli S, Franco P, et al. Paracrine recruitment and activation of fibroblasts by c-Myc expressing breast epithelial cells through the IGFs/IGF-1R axis. Int J Cancer. 2019;145:2827-2839. doi:10.1002/ijc.32613
Pacher M, Seewald MJ, Mikula M, et al. Impact of constitutive IGF1/IGF2 stimulation on the transcriptional program of human breast cancer cells. Carcinogenesis. 2007;28:49-59. doi:10.1093/carcin/bgl091
Kwon NH, Lee JY, Ryu YL, et al. Stabilization of cyclin-dependent kinase 4 by Methionyl-tRNA Synthetase in p16(INK4a)-negative cancer. ACS Pharmacol Transl Sci. 2018;1:21-31. doi:10.1021/acsptsci.8b00001
Zhou Z, Sun B, Nie A, Yu D, Bian M. Roles of aminoacyl-tRNA synthetases in cancer. Front Cell Dev Biol. 2020;8:599765. doi:10.3389/fcell.2020.599765
Mathews MB, Bernstein RM. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature. 1983;304:177-179. doi:10.1038/304177a0
Mathews MB, Reichlin M, Hughes GR, Bernstein RM. Anti-threonyl-tRNA synthetase, a second myositis-related autoantibody. J Exp Med. 1984;160:420-434. doi:10.1084/jem.160.2.420
Hirakata M, Suwa A, Nagai S, et al. Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol. 1999;162:2315-2320.
Stone KB, Oddis CV, Fertig N, et al. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum. 2007;56:3125-3131. doi:10.1002/art.22865
Darrah E, Rosen A. Granzyme B cleavage of autoantigens in autoimmunity. Cell Death Differ. 2010;17:624-632. doi:10.1038/cdd.2009.197
Jahrsdörfer B, Vollmer A, Blackwell SE, et al. Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion. Blood. 2010;115:1156-1165. doi:10.1182/blood-2009-07-235382
Cen S, Khorchid A, Javanbakht H, et al. Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1. J Virol. 2001;75:5043-5048. doi:10.1128/jvi.75.11.5043-5048.2001
Javanbakht H, Halwani R, Cen S, et al. The interaction between HIV-1 gag and human lysyl-tRNA synthetase during viral assembly. J Biol Chem. 2003;278:27644-27651. doi:10.1074/jbc.M301840200
Kobbi L, Octobre G, Dias J, Comisso M, Mirande M. Association of mitochondrial Lysyl-tRNA synthetase with HIV-1 GagPol involves catalytic domain of the synthetase and transframe and integrase domains of pol. J Mol Biol. 2011;410:875-886. doi:10.1016/j.jmb.2011.03.005
Dewan V, Wei M, Kleiman L, Musier-Forsyth K. Dual role for motif 1 residues of human lysyl-tRNA synthetase in dimerization and packaging into HIV-1. J Biol Chem. 2012;287:41955-41962. doi:10.1074/jbc.M112.421842
Duchon AA, St. Gelais C, Titkemeier N, Hatterschide J, Wu L, Musier-Forsyth K. HIV-1 exploits a dynamic multi-aminoacyl-tRNA synthetase complex to enhance viral replication. J Virol. 2017;91:e01240-17. doi:10.1128/jvi.01240-17
Clarke P, Leser JS, Bowen RA, Tyler KL. Virus-induced transcriptional changes in the brain include the differential expression of genes associated with interferon, apoptosis, interleukin 17 receptor A, and glutamate signaling as well as flavivirus-specific upregulation of tRNA synthetases. MBio. 2014;5:e00902-00914. doi:10.1128/mBio.00902-14
Marquez-Jurado S, Nogales A, Zuñiga S, Enjuanes L, Almazán F. Identification of a gamma interferon-activated inhibitor of translation-like RNA motif at the 3′ end of the transmissible gastroenteritis coronavirus genome modulating innate immune response. MBio. 2015;6:e00105. doi:10.1128/mBio.00105-15
Feng Y, Tang K, Lai Q, et al. The landscape of aminoacyl-tRNA synthetases involved in severe acute respiratory syndrome coronavirus 2 infection. Front Physiol. 2022;12:2553.
Netzer N, Goodenbour JM, David A, et al. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009;462:522-526. doi:10.1038/nature08576
Gale M Jr, Foy EM. Evasion of intracellular host defence by hepatitis C virus. Nature. 2005;436:939-945. doi:10.1038/nature04078
Lee YS, Han JM, Son SH, et al. AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2. Biochem Biophys Res Commun. 2008;371:395-400. doi:10.1016/j.bbrc.2008.04.099
Burke KP, Cox AL. Hepatitis C virus evasion of adaptive immune responses: a model for viral persistence. Immunol Res. 2010;47:216-227. doi:10.1007/s12026-009-8152-3
Kim MS, Kim S, Myung H. Degradation of AIMP1/p43 induced by hepatitis C virus E2 leads to upregulation of TGF-β signaling and increase in surface expression of gp96. PloS One. 2014;9:e96302. doi:10.1371/journal.pone.0096302
Ellis CN, LaRocque RC, Uddin T, et al. Comparative proteomic analysis reveals activation of mucosal innate immune signaling pathways during cholera. Infect Immun. 2015;83:1089-1103. doi:10.1128/iai.02765-14
Ahn YH, Park S, Choi JJ, et al. Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection. Nat Microbiol. 2016;2:16191. doi:10.1038/nmicrobiol.2016.191
Lee MS, Kwon H, Nguyen LT, et al. Shiga toxins trigger the secretion of Lysyl-tRNA synthetase to enhance proinflammatory responses. J Microbiol Biotechnol. 2016;26:432-439. doi:10.4014/jmb.1511.11056
Rycroft JA, Gollan B, Grabe GJ, et al. Activity of acetyltransferase toxins involved in salmonella persister formation during macrophage infection. Nat Commun. 2018;9:1993. doi:10.1038/s41467-018-04472-6
Kim DG, Lee JY, Kwon NH, et al. Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. Nat Chem Biol. 2014;10:29-34. doi:10.1038/nchembio.1381
Kim JH, Lee C, Lee M, et al. Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction. Nat Commun. 2017;8:732. doi:10.1038/s41467-017-00785-0
Han JM, Myung H, Kim S. Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43). Cancer Lett. 2010;287:157-164. doi:10.1016/j.canlet.2009.06.005
Lee YS, Han JM, Kang T, Park YI, Kim HM, Kim S. Antitumor activity of the novel human cytokine AIMP1 in an in vivo tumor model. Mol Cells. 2006;21:213-217.
Pines M, Spector I. Halofuginone - the multifaceted molecule. Molecules. 2015;20:573-594. doi:10.3390/molecules20010573
Keller TL, Zocco D, Sundrud MS, et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012;8:311-317. doi:10.1038/nchembio.790
Kim SH, Bae S, Song M. Recent development of aminoacyl-tRNA synthetase inhibitors for human diseases: a Future perspective. Biomolecules. 2020;10:1625. doi:10.3390/biom10121625
Shibata A, Kuno M, Adachi R, et al. Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy. PloS One. 2017;12:e0186587. doi:10.1371/journal.pone.0186587
Wu J, Subbaiah KCV, Xie LH, et al. Glutamyl-prolyl-tRNA synthetase regulates proline-rich pro-fibrotic protein synthesis during cardiac fibrosis. Circ Res. 2020;127:827-846. doi:10.1161/circresaha.119.315999
Francklyn CS, Mullen P. Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics. J Biol Chem. 2019;294:5365-5385. doi:10.1074/jbc.REV118.002956
Sundrud MS, Koralov SB, Feuerer M, et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009;324:1334-1338. doi:10.1126/science.1172638