Biol. doi:10.1038/nchem.2446, Jacob, F., and Monod, J. doi:10.1021/bi00168a002, Yamanaka, K., Nakata, H., Hohsaka, T., and Sisido, M. (2004). doi:10.1017/s1355838202029722, Serebrov, V., Vassilenko, K., Kholod, N., Gross, H. J., and Kisselev, L. (1998). those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). Nucleic acids Res. ; Lee, J.W. For instance, the efficiency of NC-AA is low due to the non-compatibility of structurally diverse NC-AA with ribosomes and elongation factors (Fujino et al., 2013). Nat. ; Goodrich, M.M. Aminoacyl-tRNA ; Arif, A.; Fox, P.L. Nat Commun. J. Exp. 2010;107:176516. doi:10.1016/0022-2836(88)90551-7, McClain, W. H., Foss, K., Jenkins, R. A., and Schneider, J. Biochemistry 37 (27), 98369842. Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage. Choi, J.W. ; Roes, M.V. 30 (1), 11101113. Z., Hori, Y., Yeung, E., Verpoorte, A., Murray, R. M., et al. doi:10.1038/nmeth877, Muramatsu, T., Nishikawa, K., Nemoto, F., Kuchino, Y., Nishimura, S., Miyazawa, T., et al. Aminoacyl-tRNA synthetases (aaRSs) play a central role in protein synthesis in all organisms. The involvement of messenger RNA (mRNA) in the central dogma was floated since 1947 but the experimental discovery came in the year 1961 by Francois Gros and Francois Jacob (Jacob and Monod, 1961). Emerging mechanisms of aminoacyl-tRNA synthetase mutations doi:10.1038/291632a0, Reynolds, N. M., Ling, J., Roy, H., Banerjee, R., Repasky, S. E., Hamel, P., et al. Cell-free Translation Reconstituted with Purified Components. 11 (6), 15691577. doi:10.1038/s42003-020-1074-2, Hill, K., and Schimmel, P. (1989). De Novo design and Synthesis of a 30-cistron Translation-Factor Module. The genetic code linkage between nucleic acids and proteins was discovered by Marshall Nirenberg in 1961 (Nirenberg and Matthaei, 1961). In one approach, [32P]-PPi is used for the reaction. Across both class I and class II, subclass A recognizes aliphatic and thiolated amino acids, subclass B recognizes charged polar amino acids, and subclass C recognizes aromatic amino acids (Rubio Gomez and Ibba, 2020). One key challenge lies in bringing together these individually engineered components. Nat. For instance, it is well established that AARSs are also involved in mRNA binding and regulation in yeast (Levi and Arava, 2019), and AARSs can autoregulate their own expression by binding to specific DNA in bacteria (Putney and Schimmel, 1981). Fournier GP, Andam CP, Alm EJ, Gogarten JP. 22 (15), 29632969. 62, 95105. Proc. Escherichia coli Seryl-tRNA Synthetase Recognizes tRNASer by its Characteristics Tertiary Structure. WebObjective: To study the clinical features of the diseases associated with aminoacyl-tRNA synthetases (ARS) deficiency. Guo, M.; Yang, X.-L.; Schimmel, P. New functions of aminoacyl-tRNA synthetases beyond translation. ; et al. doi:10.1073/pnas.0509219103, Hasegawa, T., Himeno, H., Ishikura, H., and Shimizu, M. (1989). AIMP2 aminoacyl tRNA synthetase complex interacting multifunctional protein 2 [] Gene ID: 126950511, updated on 3-Mar-2023. ML tree of the GlyRS homodimer subunit. Biochem. Proc. AARSs arose early in evolution and are believed to be a group of ancient proteins. Otani, A.; Slike, B.M. Acids Res. ; Eom, C.-Y. Expanding the Genetic Code of Escherichia coli with Phosphotyrosine. Biochimica Biophysica Acta (BBA) - Proteins Proteomics 1844 (6), 10591070. Here, we analyze publicly available genomic and transcriptomic data on human cytoplasmic and mitochondrial aaRSs across many cancer types. Amino acids radiolabeled with [3H] or [14C] are used to measure the rate of product AA-tRNAAA formation over time. Aminoacyl-tRNA synthetases (aaRSs) belong to a family of ubiquitous and essential enzymes. A Highly Flexible tRNA Acylation Method for Non-natural Polypeptide Synthesis. -tRNASRRM2RNA Identification of correct mutants of orthogonal AARS for NC-AA incorporation is largely benefited from methods such as multiplex automated genome engineering (MAGE) and phage-assisted continuous evolution (PACE). Nat. Bethesda, MD 20894, Web Policies (1991). ; Yang, X.-L. Neddylation requires glycyl-tRNA synthetase to protect activated E2. Different aminoacylation methods used for NC-AA incorporation. In the case of PheRS, PheRS competes for Tyr-tRNAPhe with EF-TU to recapture and edit the tRNA. Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive Rna 8 (4), 401411. An important role for the multienzyme aminoacyl-tRNA synthetase complex in mammalian translation and cell growth. (2018). One drawback of using radiolabeled amino acids is that attaining saturating conditions is difficult. 45 (18), 1089510905. WebSelect search scope, currently: articles+ all catalog, articles, website, & more in one search; catalog books, media & more in the Stanford Libraries' collections; Cytol. J. Biol. doi:10.1016/s0021-9258(19)44927-2, Lavickova, B., and Maerkl, S. J. Prog. (2017). Biochemistry 36 (12), 34733482. ; Lee, S.; Kim, H.K. The PURE system has been explored as a platform for producing therapeutic proteins (Cai et al., 2015; Dondapati et al., 2020) and for molecular diagnostics (Pardee et al., 2016). (2000). PLoS ONE 9 (9), e106232. Biochemistry 32 (15), 38363841. Other methods to charge tRNAs include the chemoenzymatic method, chemical method, and ribozyme method (Figure 5). These topologies and phyletic distributions are consistent with horizontal transfers from ancient, likely extinct branches of the tree of life. Bioeng. J. Chem. Biol. J. Biol. Mol. J Mol Evol. Discrimination of Cognate and Noncognate Substrates at the Active Site of Class I Lysyl-tRNA Synthetase. Five different conserved negative charges are used to identify glycine. : any of a class of amino-acid-specific enzymes that catalyze an ATP-driven reaction producing an ester linkage between a carboxyl group of an amino acid With this approach, NC-AAs can be site-specifically incorporated at multiple places (Hong et al., 2014; Martin et al., 2018). Species trees (blue) become pruned over time via extinction, while gene ancestry (red) from extinct lineages can be preserved by the HGT event, resulting in a gene ancestor predating the LUCA species ancestor. Biol. In the second step, one of the hydroxyl groups of adenosine (3-OH/2-OH) in tRNA attacks the carboxyl carbon of AAAMP intermediate resulting in the transfer of amino acid to tRNA. If these other lineages persisted for some time, HGT with the descendants of LUCA could have continued into the bacterial and archaeal lineages. Editor K. H. Nierhaus (Boston, MA: Springer), 5966. Cho, H.Y. Such pre-charged tRNAs are useful to learn more about single turnover translation. ; Alston, C.L. doi:10.1093/nar/20.9.2335, Tardif, K. D., and Horowitz, J. methods, instructions or products referred to in the content. Friedrich Miescher-aus dem Wiss. doi:10.1016/S00219258(19)36528-710.1016/s0021-9258(19)36528-7, McClain, W. H., and Foss, K. (1988a). doi:10.1073/pnas.93.14.6953, Iijima, I., and Hohsaka, T. (2009). In addition to AARS enzymes, there are other methods such as the chemoenzymatic method, chemical method, and ribozyme-based approaches for acylation to charge tRNA with NC-AAs. 33 (8), 25952602. E.coliinitiator tRNA Analogs with Different Nucleotides in the Discriminator Base Position. Biol. Nucl. Another approach for incorporating NC-AA that avoids the use of AARS altogether is performed by ribozymes called flexizymes pioneered by Prof. Hiroaki Suga. Biol. Soc. Rapid chemical quench and stopped-flow fluorimetry are generally used to study AARSs. Genetic Regulatory Mechanisms in the Synthesis of Proteins. HHS Vulnerability Disclosure, Help Cambridge, United Kingdom: The Francis Crick Papers. BioDrugs 34 (3), 327348. Selection for Active E. coli tRNA(Phe) Variants from a Randomized Library Using Two Proteins. J. Biol. An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. (2018). Proc. doi:10.1084/jem.79.2.137, Awai, T., Ichihashi, N., and Yomo, T. (2015). Identity Determinants of E. coli tRNAVal. aaRSs have well-established links to cancer already, although it is unclear in some cases if their effect is linked to their non-canonical functions or conserved role in translation. Recognition of tRNATyr by Tyrosyl-tRNA Synthetase. doi:10.1016/j.chembiol.2016.11.012, Kawakami, T., Ishizawa, T., and Murakami, H. (2013). They constitute a family of enzymes integrating the two levels of cellular organization: nucleic acids and proteins. A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics. School of Engineering, Institute of Bioengineering, cole Polytechnique Fdrale de Lausanne, Lausanne, Switzerland. For example, substrate-binding order in the active site, formation, and consumption of intermediates can be studied by pre-steady state kinetics. Cell 165 (5), 12551266. U.S.A. 116 (13), 58925901. Ribosomal Incorporation of Consecutive -Amino Acids. Changing the Acceptor Identity of a Transfer RNA by Altering Nucleotides in a Variable Pocket. The tRNA structure consists of the following: the anticodon arm, D-arm, T-arm, acceptor stem, and the variable arm. You seem to have javascript disabled. Glycyl-tRNA synthetase is a class II aminoacyl-tRNA synthetase that catalyzes the synthesis of glycyl-tRNA, which is required to insert glycine into proteins. Conclusions: Cell-free Gene-Regulatory Network Engineering with Synthetic Transcription Factors. They catalyse the esterification reactions that link amino acids with cognate tRNAs bearing the correct anticodon triplet to ensure the accurate transfer of information directed by the genetic code (Schimmel, 1987). B., Bhumkar, A., Giles, N., Sierecki, E., and Gambin, Y. the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, Construction of Escherichia coli Amber Suppressor tRNA Genes. Aminoacyl Am. Background: 113 (2), 292300. These expressed proteins were functional with activity on par with their native counterparts purified from E. coli. Hyeon, D.Y. WebTo expand the genetic code, modified tRNAs, codons, and tRNA synthetases are introduced into the cell on plasmids and the new amino acid is introduced in the media. U.S.A. 90 (14), 67766780. doi:10.1002/j.1460-2075.1993.tb05958.x, Peterson, E. T., and Uhlenbeck, O. C. (1992). Furthermore, cell-free systems are advantageous to study non-canonical functions of AARS in addition to tRNA charging. doi:10.1016/j.chembiol.2011.08.008, Moore, S. J., MacDonald, J. T., Wienecke, S., Ishwarbhai, A., Tsipa, A., Aw, R., et al. doi:10.1038/nchembio.2514, Wan, W., Tharp, J. M., and Liu, W. R. (2014). doi:10.1073/pnas.1715806115, Morimoto, J., Hayashi, Y., Iwasaki, K., and Suga, H. (2011). MAGE is an in vivo continuous platform for large-scale introduction of allelic replacement in chromosomal DNA achieved by inactivation of the mismatch repair system by the mutS gene and -Red recombinase systems containing exo, beta, and gam proteins. Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains. ; et al. Kwon, N.H.; Kang, T.; Lee, J.Y. Pyrrolysyl synthetase (PylRS) is one such AARS which had limited use due to difficulties in purification. Cell-free systems opened up the possibility to work with a range of organisms from conventional model organisms such as E. coli and yeast to more un-conventional systems such as Bacillus megaterium (Moore et al., 2018), Clostridium autoethanogenum (Krger et al., 2020), and eukaryote-derived systems such as rabbit reticulocyte lysate (Gagoski et al., 2016). ; Cho, H.Y. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We use cookies on our website to ensure you get the best experience. Proc. The complete list of identity elements and their location in the tRNA for each AARS from E. coli is provided in Table 1. ; formal analysis, J.W., I.V., A.D.; writingoriginal draft preparation, J.W., I.V. Enzymatic Carboxyl Activation of Amino Acids. The Role of Aminoacyl-tRNA Synthetases in Genetic Diseases doi:10.1021/bi00417a023, Liu, H., Peterson, R., Kessler, J., and Musier-Forsyth, K. (1995). Zosta lepszym graczem. Probing the Metal Binding Sites of Escherichia coli Isoleucyl-tRNA Synthetase. For residue-specific incorporation, all of the sense codons for a particular amino acid are reassigned to the NC-AA. Gene Lim, S.; Cho, H.Y. Abstract. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. 5 (9), 929935. Stopped-flow fluorimetry is a continuous assay and provides an indirect readout of reaction progress. For transfer RNA (tRNA), Crick hypothesized the existence of adaptor molecules, which are unstable and help carry the amino acids to the ribosomes in the cytoplasm for protein synthesis (Crick, 1955). doi:10.1021/acssynbio.6b00342, Li, J., Zhang, C., Huang, P., Kuru, E., Forster-Benson, E. T. C., Li, T., et al. Unexpected Instabilities Explain Batchtobatch Variability in Cellfree Protein Expression Systems. The most commonly used identity elements are the anticodon bases 34, 35, and 36 in the anticodon arm and the discriminatory base 73 in the acceptor stem of the tRNA. doi:10.1093/nar/19.23.6379, Himeno, H., Hasegawa, T., Ueda, T., Watanabe, K., Miura, K.-i., and Shimizu, M. (1989). We examined whether there was any apparent accumulation of mutations affecting the aaRSs using cBioPortal (, The aaRSs are not as heavily mutated as other oncogenes and tumor suppressors, presumably because of the selective pressure to maintain their catalytic function in charging tRNAs. Enzymatic Aminoacylation of an Eight-Base-Pair Microhelix with Histidine. 10 (1), 1325. doi:10.1038/s41467-019-09147-4, Beuning, P. J., and Musier-Forsyth, K. (2001). Chem. Editing Mechanisms in Protein Synthesis. Epub 2020 Jun 11. doi:10.1038/321213a0, Normanly, J., Ollick, T., and Abelson, J. Mol. Biased gene transfer in microbial evolution. Nature 472 (7344), 499503. Biol. 590, 30403047. doi:10.1021/bi952889f, Yan, W., and Francklyn, C. (1994). 8 (4), 317325. In site-specific incorporation, a NC-AA is incorporated into a specific location whereas in residue-specific incorporation a NC-AA is incorporated into all sites encoded by a specific codon. Branch colors depict the taxonomy of, ML tree showing the common and rare types of SerRS and ThrRS. WebGene provides a unified query environment for genes defined by sequence and/or in NCBI's Map Viewer. ACS Synth. ; Goodrich, D.W. This technique has opened up the possibility to charge any tRNA with nearly any amino acid and thereby reassigning any codon with NC-AAs. In the following, a brief history of the discovery of key steps and components involved in the central dogma is discussed. Biol. J. Biol. Conversion of a Methionine Initiator tRNA into a Tryptophan-Inserting Elongator tRNA In Vivo. Nagy, .; Lnczky, A.; Menyhrt, O.; Gyrffy, B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. On the other hand, proteins were conclusively proved not to be the genetic material by Hersley and Chase in 1952 (Hershey and Chase, 1952), and the work by Rosaling Franklin, Maurice Wilkins, James Watson, and Francis Crick leading to the 1953 paper describing the three-dimensional structure of the genetic material DNA (Watson and Crick, 1953), and its double-helical structure with base-pairing according to Chargaffs rules (Chargaff, 1950). Currently, a more sophisticated one-pot method for in vitro tRNA synthesis has been developed (Korenci, Sll, and Ambrogelly, 2002). 292 (36), 1513415142. Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. J. Biol. CFPS systems eliminate some of the stringency associated with in vivo translation and simplified engineering of the protein synthesis process to some extent. These methods helped generate and screen a large library of AARS mutants in a short period, thereby saving time and effort. Res. Conformational Change of tRNA upon Interaction of the Identity-Determinant Set with Aminoacyl-tRNA Synthetase, in The Translational Apparatus: Structure, Function, Regulation, Evolution. Nat Rev Microbiol. Med. ; Kim, D.G. Biochemistry 31 (42), 1038010389. ; Passos, D.T. Specific interactions are mediated by identity elements such as modified nucleotides, conserved residues, base stacking, and different tRNA arm lengths. ; et al. Pre-transfer editing is seen in both AARS classes. Exploring the Substrate Range of Wild-type Aminoacyl-tRNA Synthetases. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. 268 (26), 1939819402. noun. From a theoretical point of view, there are 64 (43) different codon sequences available. ATP and amino acids form aminoacyl adenylate intermediate (AAAMP) with the release of pyrophosphate (PPi). Aminoacyl-tRNA Synthetases. In Vitro incorporation of Nonnatural Amino Acids into Protein Using tRNACys-Derived Opal, Ochre, and Amber Suppressor tRNAs. J. Biol. R213I Mutation in Release Factor 2 (RF2) Is One Step Forward for Engineering an Omnipotent Release Factor in Bacteria Escherichia coli. Activated tRNA-AA binds with the elongation factor, EF-TU, and when reaching the ribosome participates in translation. Glycyl Transfer Ribonucleic Acid Synthetase from Escherichia coli. official website and that any information you provide is encrypted Since steady-state kinetics are used generally, parameters obtained can be compared across systems. Soc. Development of a Clostridia-Based Cell-free System for Prototyping Genetic Parts and Metabolic Pathways. tRNA synthetase counteracts c-Myc to develop functional vasculature. The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data: Figure 1. WebAminoacylation, the attachment of an amino acid to a tRNA, is typically a two-step process catalyzed by the aminoacyl-tRNA synthetases. ATP and amino acid bind to the AARS enzyme triggering a nucleophilic attack of the amino acid carboxyl oxygen to the -phosphate group of ATP. A., Takahashi, M. K., Braff, D., Lambert, G., Lee, J. W., et al. doi:10.1006/jmbi.1994.1184, Nureki, O., Niimi, T., Muto, Y., Kanno, H., Kohno, T., Muramatsu, T., et al. doi:10.1093/nar/22.15.2963, Bryson, D. I., Fan, C., Guo, L.-T., Miller, C., Sll, D., and Liu, D. R. (2017). ; Kwon, N.H.; Shin, Y.K. Natl. KM and Kcat values of amino acids for AARS from E. coli unless mentioned otherwise. Such a modified tRNA allowed incorporating NC-AAs with better efficiency in an E. coli in vitro translation system (Hohsaka et al., 2001). ; Ahn, H.W. Chem. The modified amino acid was shown to be incorporated at multiple instances and up to two distinct NC-AA were incorporated with this approach. Aminoacyl tRNA synthetases (AARSs) and tRNAs are key components involved in translation and thus protein synthesis. J. Mol. Katsyv, I.; Wang, M.; Song, W.M. Cell-free transcription and translation systems have enormous potential to overcome the limits of cell-based protein synthesis and could become the next generation platform for protein engineering that can go well beyond the scope of what could be accomplished in a cellular environment. Recognition Nucleotides of Escherichia coli tRNALeu and its Elements Facilitating Discrimination from tRNASer and tRNATyr. EMBO J. Transfer RNA Synthesis In Vitro. It does so by catalyzing the transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. doi:10.1016/j.synbio.2019.10.003, Ebel, J. P., Gieg, R., Bonnet, J., Kern, D., Befort, N., Bollack, C., et al. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into This way, the tRNA pool directing the translation process can in principle be fully customized. Proc. In terms of reaction catalysis, the rate-limiting steps between both classes differ as well. Natl. The translation process bridges the nucleotide world and the amino acid world. ; Lee, S.W. U.S.A. 89 (19), 92629266. 137 (13), 44044413. ; Kang, B.S. Synthetic Microbial Consortia Enable Rapid Assembly of Pure Translation Machinery. Transcribed tRNAs were shown to be produced in full length and aminoacylated by AARSs. FOIA Half-life values of tRNA-AA from E. coli. Overexpressed tryptophanyl-tRNA synthetase, an angiostatic protein, enhances oral cancer cell invasiveness. In vitro synthesis of functional tRNA has made it easier to study interactions of tRNA with other components such as mRNA (Fauzi, Jack, and Hines, 2005) and AARSs (Wang et al., 2015), to investigate tRNA stability in vitro (Serebrov et al., 1998), and to determine mutational effects on tRNA function (Tamura et al., 1992). Ijms 20 (9), 2343. doi:10.3390/ijms20092343, Bedouelle, H. (1990). 9 (3), 145153. 4 (3), 207212. Proc. 12.5: Ribosomes and Protein Synthesis - Biology LibreTexts Species Specificity of Amino Acid Acceptor Ribonucleic Acid and Aminoacyl Soluble Ribonucleic Acid Synthetases. Most AARSs use one of these editing mechanisms, but some AARS such as LeuRS and ValRS use both mechanisms. AARSs in group 2 have identity elements located only in the acceptor stem and anticodon arm. J. Biol. doi:10.1126/science.aat0971, Hou, Y.-M., and Schimmel, P. (1988). These enzymes first bind and hydrolyze ATP to catalyze a high-energy bond between an amino acid and adenosine monophosphate (AMP); a pyrophosphate molecule is expelled in this The value represents the spontaneous hydrolysis rate of tRNA-AA at neutral or alkaline pH in a high ionic condition at 37C. Liu, J.; Lichtenberg, T.; Hoadley, K.A. The Structure of Yeast Nucleic Acid. Wang, J.; Vallee, I.; Dutta, A.; Wang, Y.; Mo, Z.; Liu, Z.; Cui, H.; Su, A.I. ; Kishi, S.; Yang, X.L. Editing activity can be divided into pre-transfer editing and post-transfer editing. Bioeng. (1973). -, Rothman DH, Fournier GP, French KL, Alm EJ, Boyle EA, Cao C, et al. Rapid Determination of Nucleotides that Define tRNA(Gly) Acceptor Identity. The development of an orthogonal translation system requires a coordinated effect at every level of protein expression. Results: The different observed protein subunit configurations are depicted on the right, using the same color scheme. Kim, D.G. Disclaimer. The .gov means its official. This is most apparent in the evolutionary histories of seryl-tRNA synthetase and threonyl-tRNA synthetase protein families, each containing highly divergent "rare" forms, as well as the sparse phylogenetic distributions of pyrrolysyl-tRNA synthetase, and the bacterial heterodimeric form of glycyl-tRNA synthetase. 20 (9), 23352339. This system is used for easy detection of in vitro protein expression. (2015). KM refers to affinity of the enzyme to the substrate. doi:10.1016/0014-5793(95)00132-S, Gubbens, J., Kim, S. J., Yang, Z., Johnson, A. E., and Skach, W. R. (2010). Cell-free biology can be defined as, the reproduction, study, and exploitation of complex biological processes without intact cells (Swartz, 2006). (A) AARS aminoacylation process. Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components. Bioeng. Branch colors depict the taxonomy of PylRS lineages, with Euryarchaeota (red), Firmicutes (blue) and Deltaproteobacteria (magenta). ; Kim, J.H. Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for (1992). Phylogenetic Signal, Congruence, and Uncertainty across Bacteria and Archaea. Proteins were purified using His-tagbased affinity chromatography (Shimizu et al., 2001). Splicing variant of AIMP2 as an effective target against chemoresistant ovarian cancer. Some aaRSs in higher eukaryotes have been found to possess non-canonical functions and to be involved in numerous cellular processes [ 1 ]. Kim, D.; Kwon, N.H.; Kim, S. Association of Aminoacyl-tRNA Synthetases with Cancer.