DARS (gene) explained

Aspartyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the DARS gene.^{[1] [2]}

Aspartyl-tRNA synthetase (DARS) is part of a multienzyme complex of aminoacyl-tRNA synthetases. Aspartyl-tRNA synthetase charges its cognate tRNA with aspartate during protein biosynthesis.^[2]

Clinical significance

Mutations in DARS have been identified as the cause of leukoencephalopathy, hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL).^[3]

See also

• Aspartate-tRNA ligase

Further reading

• Norcum MT . Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents. . J. Biol. Chem. . 266 . 23 . 15398–405 . 1991 . 10.1016/S0021-9258(18)98629-1 . 1651330 . free .
• Reed VS, Wastney ME, Yang DC . Mechanisms of the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to the elongation factor 1 alpha. . J. Biol. Chem. . 269 . 52 . 32932–6 . 1995 . 10.1016/S0021-9258(20)30080-6 . 7806521 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Escalante C, Yang DC . Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix . J. Biol. Chem. . 268 . 8 . 6014–23 . 1993 . 10.1016/S0021-9258(18)53420-7 . 8449960 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Quevillon S, Robinson JC, Berthonneau E . Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein . J. Mol. Biol. . 285 . 1 . 183–95 . 1999 . 9878398 . 10.1006/jmbi.1998.2316 . etal.
• Rho SB, Kim MJ, Lee JS . Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex . Proc. Natl. Acad. Sci. U.S.A. . 96 . 8 . 4488–93 . 1999 . 10200289 . 10.1073/pnas.96.8.4488 . 16359 . 1999PNAS...96.4488R . etal. free .
• Kang J, Kim T, Ko YG . Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases . J. Biol. Chem. . 275 . 41 . 31682–8 . 2000 . 10913161 . 10.1074/jbc.M909965199 . etal. free .
• Sang Lee J, Gyu Park S, Park H . Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex . Biochem. Biophys. Res. Commun. . 291 . 1 . 158–64 . 2002 . 11829477 . 10.1006/bbrc.2002.6398 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Cheong HK, Park JY, Kim EH . Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function . Int. J. Biochem. Cell Biol. . 35 . 11 . 1548–57 . 2004 . 12824064 . 10.1016/S1357-2725(03)00070-0 . 39165251 . etal.
• Bouwmeester T, Bauch A, Ruffner H . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway . Nat. Cell Biol. . 6 . 2 . 97–105 . 2004 . 14743216 . 10.1038/ncb1086 . 11683986 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Bonnefond L, Fender A, Rudinger-Thirion J . Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS . Biochemistry . 44 . 12 . 4805–16 . 2005 . 15779907 . 10.1021/bi047527z . etal.
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Tu LC, Yan X, Hood L, Lin B . Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells . Mol. Cell. Proteomics . 6 . 4 . 575–88 . 2007 . 17220478 . 10.1074/mcp.M600249-MCP200 . free .

Notes and References

1. Jacobo-Molina A, Peterson R, Yang DC . cDNA sequence, predicted primary structure, and evolving amphiphilic helix of human aspartyl-tRNA synthetase . J Biol Chem . 264 . 28 . 16608–12 . Oct 1989 . 10.1016/S0021-9258(19)84749-X . 2674137 . free .
2. Web site: Entrez Gene: DARS aspartyl-tRNA synthetase.
3. Taft RJ, Vanderver A, Leventer RJ, Damiani SA, Simons C, Grimmond SM, Miller D, Schmidt J, Lockhart PJ, Pope K, Ru K, Crawford J, Rosser T, de Coo IF, Juneja M, Verma IC, Prabhakar P, Blaser S, Raiman J, Pouwels PJ, Bevova MR, Abbink TE, van der Knaap MS, Wolf NI . Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity . American Journal of Human Genetics . 2013 . 10.1016/j.ajhg.2013.04.006 . 92 . 5 . 774–780 . 23643384 . 3644624.