Table of Contents Author Guidelines Submit a Manuscript
International Journal of Cell Biology
Volume 2014, Article ID 787956, 11 pages
http://dx.doi.org/10.1155/2014/787956
Review Article

The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes

Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Mitochondrial Disorders in Children, IRCCS Foundation Neurological Institute “C. Besta”, Via Temolo 4, 20126 Milan, Italy

Received 13 September 2013; Accepted 1 December 2013; Published 4 February 2014

Academic Editor: R. Seger

Copyright © 2014 Daria Diodato et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. W. Taylor and D. M. Turnbull, “Mitochondrial DNA mutations in human disease,” Nature Reviews Genetics, vol. 6, no. 5, pp. 389–402, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Ghezzi and M. Zeviani, “Assembly factors of human mitochondrial respiratory chain complexes: physiology and pathophysiology,” Advances in Experimental Medicine and Biology, vol. 748, pp. 65–106, 2012. View at Google Scholar
  3. P. Smits, J. Smeitink, and L. van den Heuvel, “Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 737385, 24 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Watanabe, “Unique features of animal mitochondrial translation systems: the non-universal genetic code, unusual features of the translational apparatus and their relevance to human mitochondrial diseases,” Proceedings of the Japan Academy Series B, vol. 86, no. 1, pp. 11–39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Liu and L. Spremulli, “Interaction of mammalian mitochondrial ribosomes with the inner membrane,” Journal of Biological Chemistry, vol. 275, no. 38, pp. 29400–29406, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. V. Ramakrishnan, “Ribosome structure and the mechanism of translation,” Cell, vol. 108, no. 4, pp. 557–572, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Marintchev and G. Wagner, “Translation initiation: structures, mechanisms and evolution,” Quarterly Reviews of Biophysics, vol. 37, no. 3-4, pp. 197–284, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. G. Bertram, S. Innes, O. Minella, J. P. Richardson, and I. Stansfield, “Endless possibilities: translation termination and stop codon recognition,” Microbiology, vol. 147, no. 2, pp. 255–269, 2001. View at Google Scholar · View at Scopus
  9. A. Zeharia, A. Shaag, O. Pappo et al., “Acute infantile liver failure due to mutations in the TRMU gene,” American Journal of Human Genetics, vol. 85, no. 3, pp. 401–407, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. D. Ghezzi, E. Baruffini, T. B. Haack et al., “Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis,” The American Journal of Human Genetics, vol. 90, pp. 1079–1087, 2012. View at Google Scholar
  11. J. A. M. Smeitink, O. Elpeleg, H. Antonicka et al., “Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs,” American Journal of Human Genetics, vol. 79, no. 5, pp. 869–877, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Valente, V. Tiranti, R. M. Marsano et al., “Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu,” American Journal of Human Genetics, vol. 80, no. 1, pp. 44–58, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Ibba and D. Soll, “Aminoacyl-tRNA synthesis,” Annual Review of Biochemistry, vol. 69, pp. 617–650, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Nagao, T. Suzuki, T. Katoh, Y. Sakaguchi, and T. Suzuki, “Biogenesis of glutaminyl-mt tRNAGln in human mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 38, pp. 16209–16214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Li and M.-X. Guan, “Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes,” Molecular and Cellular Biology, vol. 30, no. 9, pp. 2147–2154, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. P. King and G. Attardi, “Post-transcriptional regulation of the steady-state levels of mitochondrial tRNAs in HeLa cells,” Journal of Biological Chemistry, vol. 268, no. 14, pp. 10228–10237, 1993. View at Google Scholar · View at Scopus
  17. K. Beebe, M. Mock, E. Merriman, and P. Schimmel, “Distinct domains of tRNA synthetase recognize the same base pair,” Nature, vol. 451, no. 7174, pp. 90–93, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Bonnefond, A. Fender, J. Rudinger-Thirion, R. Giegé, C. Florentz, and M. Sissler, “Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS,” Biochemistry, vol. 44, no. 12, pp. 4805–4816, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. E. V. Smirnova, V. A. Lakunina, I. Tarassov, I. A. Krasheninnikov, and P. A. Kamenski, “Noncanonical functions of aminoacyl-tRNA synthetases,” Biochemistry, vol. 77, no. 1, pp. 15–25, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Konovalova and H. Tyynismaa, “Mitochondrial aminoacyl-tRNA synthetases in human disease,” Molecular Genetics and Metabolism, vol. 108, no. 4, pp. 206–211, 2013. View at Google Scholar
  21. G. C. Scheper, T. van der Klok, R. J. van Andel et al., “Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation,” Nature Genetics, vol. 39, no. 4, pp. 534–539, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Van Berge, S. Dooves, C. G. M. Van Berkel, E. Polder, M. S. Van Der Knaap, and G. C. Scheper, “Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA,” Biochemical Journal, vol. 441, no. 3, pp. 955–962, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. P. Labauge, I. Dorboz, E. Eymard-Pierre, O. Dereeper, and O. Boespflug-Tanguy, “Clinically asymptomatic adult patient with extensive LBSL MRI pattern and DARS2 mutations,” Journal of Neurology, vol. 258, no. 2, pp. 335–337, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Sharma, N. Sankhyan, A. Kumar, G. C. Scheper, M. S. Van Der Knaap, and S. Gulati, “Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate,” Journal of Child Neurology, vol. 26, no. 6, pp. 773–776, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. P. Isohanni, T. Linnankivi, J. Buzkova et al., “DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis,” Journal of Medical Genetics, vol. 47, no. 1, pp. 66–70, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. N. Miyake, S. Yamashita, K. Kurosawa et al., “A novel homozygous mutation of DARS2 may cause a severe LBSL variant,” Clinical Genetics, vol. 80, no. 3, pp. 293–296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Yamashita, N. Miyake, N. Matsumoto et al., “Neuropathology of leukoencephalopathy with brainstem and spinal cord involvement and high lactate caused by a homozygous mutation of DARS2,” Brain and Development, vol. 35, no. 4, pp. 312–316, 2013. View at Google Scholar
  28. M. Synofzik, J. Schicks, T. Lindig et al., “Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2 mutation,” Journal of Medical Genetics, vol. 48, no. 10, pp. 713–715, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Edvardson, A. Shaag, O. Kolesnikova et al., “Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia,” American Journal of Human Genetics, vol. 81, no. 4, pp. 857–862, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Rankin, R. Brown, W. B. Dobyns et al., “Pontocerebellar hypoplasia type 6: a British case with PEHO-like features,” American Journal of Medical Genetics, Part A, vol. 152, no. 8, pp. 2079–2084, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. D. Cassandrini, M. R. Cilio, M. Bianchi et al., “Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients,” Journal of Inherited Metabolic Disease, vol. 36, no. 1, pp. 43–53, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Namavar, P. G. Barth, P. R. Kasher et al., “Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia,” Brain, vol. 134, no. 1, pp. 143–156, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. L. G. Riley, S. Cooper, P. Hickey et al., “Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia - MLASA syndrome,” American Journal of Human Genetics, vol. 87, no. 1, pp. 52–59, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Shahni, Y. Wedatilake, M. A. Cleary, K. J. Lindley, K. R. Sibson, and S. Rahman, “A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations,” American Journal of Medical Genetics Part A, vol. 161, no. 9, pp. 2334–2338, 2013. View at Google Scholar
  35. F. Sasarman, T. Nishimura, I. Thiffault, and E. A. Shoubridge, “A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia,” Human Mutation, vol. 33, no. 8, pp. 1201–1206, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. R. Belostotsky, E. Ben-Shalom, C. Rinat et al., “Mutations in the mitochondrial Seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome,” American Journal of Human Genetics, vol. 88, no. 2, pp. 193–200, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Rivera, E. Martin-Hernandez, A. Delmiro et al., “A new mutation in the gene encoding mitochondrial seryl-tRNA synthetase as a cause of HUPRA syndrome,” BMC Nephrology, vol. 13, no. 14, p. 195, 2013. View at Publisher · View at Google Scholar
  38. A. Götz, H. Tyynismaa, L. Euro et al., “Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy,” American Journal of Human Genetics, vol. 88, no. 5, pp. 635–642, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Diodato, L. Melchionda, T. B. Haack et al., “Mutations in mitochondrial aminoacyl tRNA synthetases identified by exome-sequencing,” European Journal of Human Genetics, vol. 21, supplement 2, p. 244, 2013. View at Google Scholar
  40. V. Bayat, I. Thiffault, M. Jaiswal et al., “Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans,” PLoS Biology, vol. 10, no. 3, Article ID e1001288, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. S. B. Pierce, K. M. Chisholm, E. D. Lynch et al., “Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 16, pp. 6543–6548, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. S. B. Pierce, K. Gersak, R. Michaelson-Cohen et al., “Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome,” The American Journal of Human Genetics, vol. 92, pp. 614–620, 2013. View at Google Scholar
  43. H. E. Shamseldin, M. Alshammari, T. Al-Sheddi et al., “Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes,” Journal of Medical Genetics, vol. 49, pp. 234–241, 2012. View at Google Scholar
  44. J. M. Elo, S. S. Yadavalli, L. Euro et al., “Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy,” Human Molecular Genetics, vol. 21, pp. 4521–4529, 2012. View at Google Scholar
  45. A. Almalki, C. L. Alston, A. Parker et al., “Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency,” Biochim Biophys Acta, vol. 1842, no. 1, pp. 56–64, 2013. View at Publisher · View at Google Scholar
  46. M. E. Steenweg, D. Ghezzi, T. Haack et al., “Leukoencephalopathy with thalamus and brainstem involvement and high lactate “LTBL” caused by EARS2 mutations,” Brain, vol. 135, no. 5, pp. 1387–1394, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Talim, A. Pyle, H. Griffin et al., “Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation,” Brain, vol. 136, part 2, p. e228, 2012. View at Publisher · View at Google Scholar
  48. A. Antonellis, R. E. Ellsworth, N. Sambuughin et al., “Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V,” American Journal of Human Genetics, vol. 72, no. 5, pp. 1293–1299, 2003. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Del Bo, F. Locatelli, S. Corti et al., “Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation,” Neurology, vol. 66, no. 5, pp. 752–754, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Antonellis, S.-Q. Lee-Lin, A. Wasterlain et al., “Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons,” Journal of Neuroscience, vol. 26, no. 41, pp. 10397–10406, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. W. W. Motley, K. L. Seburn, M. H. Nawaz et al., “Charcot-marie-tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels,” PLoS Genetics, vol. 7, no. 12, Article ID e1002399, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. K. L. Seburn, L. A. Nangle, G. A. Cox, P. Schimmel, and R. W. Burgess, “An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model,” Neuron, vol. 51, no. 6, pp. 715–726, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Jordanova, J. Irobi, F. P. Thomas et al., “Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy,” Nature Genetics, vol. 38, no. 2, pp. 197–202, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Latour, C. Thauvin-Robinet, C. Baudelet-Méry et al., “A major determinant for binding and aminoacylation of tRNAAla in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease,” American Journal of Human Genetics, vol. 86, no. 1, pp. 77–82, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. H. M. McLaughlin, R. Sakaguchi, W. Giblin et al., “A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with charcot-marie-tooth disease type 2N (CMT2N),” Human Mutation, vol. 33, no. 1, pp. 244–253, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Vester, G. Velez-Ruiz, H. M. McLaughlin et al., “A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo,” Human Mutation, vol. 34, pp. 191–199, 2013. View at Google Scholar
  57. H. M. McLaughlin, R. Sakaguchi, C. Liu et al., “Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy,” American Journal of Human Genetics, vol. 87, no. 4, pp. 560–566, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. R. L. P. Santos-Cortez, K. Lee, Z. Azeem et al., “Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89,” The American Journal of Human Genetics, vol. 93, pp. 132–140, 2013. View at Google Scholar
  59. K.-J. Chang, G. Lin, L.-C. Men, and C.-C. Wang, “Redundancy of non-AUG initiators: a clever mechanism to enhance the efficiency of translation in yeast,” Journal of Biological Chemistry, vol. 281, no. 12, pp. 7775–7783, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Achilli, V. Bros-Facer, H. P. Williams 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,” DMM Disease Models and Mechanisms, vol. 2, no. 7-8, pp. 359–373, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. S. A. Dogan, C. Pujol, and A. Trifunovic, “Mitochondrial aspartyl-tRNA synthetase (DARS2) deficiency in mice,” Experimental Gerontology, vol. 48, p. 696, 2013. View at Publisher · View at Google Scholar
  62. E. Baruffini, C. Dallabona, F. Invernizzi et al., “MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast,” Human Mutation, vol. 34, no. 11, pp. 1501–1509, 2013. View at Publisher · View at Google Scholar
  63. K. A. Dittmar, J. M. Goodenbour, and T. Pan, “Tissue-specific differences in human transfer RNA expression,” PLoS Genetics, vol. 2, no. 12, pp. 2107–2115, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. R. J. Taft, A. Vanderver, R. J. Leventer et al., “Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity,” The American Journal of Human Genetics, vol. 92, pp. 774–780, 2013. View at Google Scholar
  65. R. L. Hurto, “Unexpected functions of tRNA and tRNA processing enzymes,” Advances in Experimental Medicine and Biology, vol. 722, pp. 137–155, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Klipcan and M. Safro, “Amino acid biogenesis, evolution of the genetic code and aminoacyl-tRNA synthetases,” Journal of Theoretical Biology, vol. 228, no. 3, pp. 389–396, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. C. De Luca, Y. Zhou, A. Montanari et al., “Can yeast be used to study mitochondrial diseases? Biolistic tRNA mutants for the analysis of mechanisms and suppressors,” Mitochondrion, vol. 9, no. 6, pp. 408–417, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. S. G. Park, P. Schimmel, and S. Kim, “Aminoacyl tRNA synthetases and their connections to disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 32, pp. 11043–11049, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Montanari, C. De Luca, L. Frontali, and S. Francisci, “Aminoacyl-tRNA synthetases are multivalent suppressors of defects due to human equivalent mutations in yeast mt tRNA genes,” Biochimica et Biophysica Acta, vol. 1803, no. 9, pp. 1050–1057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Francisci, A. Montanari, C. De Luca, and L. Frontali, “Peptides from aminoacyl-tRNA synthetases can cure the defects due to mutations in mt tRNA genes,” Mitochondrion, vol. 11, no. 6, pp. 919–923, 2011. View at Publisher · View at Google Scholar · View at Scopus