A new mechanism for mtDNA pathogenesis: Impairment of post-transcriptional maturation leads to severe depletion of mitochondrial tRNASer(UCN) caused by T7512C and G7497A point mutations

Nucleic Acids Research

Volumn 33, Issue 17, 2005, Pages 5647-5658

  Möllers, Myriam ^a   Maniura Weber, Katharina ^a,e   Kiseljakovic, Emina ^a,b   Bust, Maria ^a   Hayrapetyan, Armine ^c   Jaksch, Michaela ^d   Helm, Mark ^c   Wiesner, Rudolf J ^a   von Kleist Retzow, Jürgen Christoph ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

^b UNIVERSITY OF SARAJEVO   (Bosnia and Herzegovina)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d Institute of Clinical Chemistry Molecular Diagnostics and Mitochondrial Genetics   (Germany)

^e SWISS FEDERAL LABORATORIES FOR MATERIALS SCIENCE AND TECHNOLOGY   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

MITOCHONDRIAL DNA; MITOCHONDRIAL PROTEIN; NUCLEASE; TRANSFER RNA; CYTOCHROME C OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); RNA; RNA PRECURSOR; RNA, MITOCHONDRIAL; SERINE TRANSFER RNA;

ACYLATION; ARTICLE; CARCINOGENESIS; CASE REPORT; CONTROLLED STUDY; CYBRID; ELECTROPHORETIC MOBILITY; ENZYME DEGRADATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MUTANT; NORTHERN BLOTTING; OSTEOSARCOMA; POINT MUTATION; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN PROCESSING; PROTEIN SYNTHESIS; RESPIRATORY CHAIN; STEADY STATE; AMINOACYLATION; BIOSYNTHESIS; CELL LINE; CHEMISTRY; CHILD; DISORDERS OF MITOCHONDRIAL FUNCTIONS; GENETICS; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; RNA PROCESSING; RNA STABILITY;

AMINOACYLATION; BASE SEQUENCE; CELL LINE; CHILD; CHILD, PRESCHOOL; DNA, MITOCHONDRIAL; ELECTRON TRANSPORT COMPLEX I; ELECTRON TRANSPORT COMPLEX IV; HUMANS; MALE; MITOCHONDRIAL DISEASES; MITOCHONDRIAL PROTEINS; MOLECULAR SEQUENCE DATA; POINT MUTATION; RNA; RNA PRECURSORS; RNA PROCESSING, POST-TRANSCRIPTIONAL; RNA STABILITY; RNA, TRANSFER, SER;

EID: 26944473679     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gki876     Document Type: Article

References (49)

1. Florentz,C., Sohm,B., Tryoen-Toth,P., Putz,J. and Sissler,M. (2003) Human mitochondrial tRNAs in health and disease. Cell Mol. Life Sci., 60, 1356-1375.
2. Florentz,C. and Sissler,M. (2001) Disease-related versus polymorphic mutations in human mitochondrial tRNAs. Where is the difference? EMBO Rep., 2, 481-486.
3. Chomyn,A., Enriquez,J.A., Micol,V., Fernandez-Silva,P. and Attardi,G. (2000) The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome-associated human mitochondrial tRNALeu(UUR) mutation causes aminoacylation deficiency and concomitant reduced association of mRNA with ribosomes. J. Biol. Chem., 275, 19198-19209.
4. El Meziane,A., Lehtinen,S.K., Holt,I.J. and Jacobs,H.T. (1998) Mitochondrial tRNALeu isoforms in lung carcinoma cybrid cells containing the np 3243 mtDNA mutation. Hum. Mol. Genet., 7, 2141-2147.
5. Yasukawa,T., Suzuki,T., Ueda,T., Ohta,S. and Watanabe,K. (2000) Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. J. Biol. Chem., 275, 4251-4257.
6. Dunbar,D.R., Moonie,P.A., Zeviani,M. and Holt,I.J. (1996) Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids. Hum. Mol. Genet, 5, 123-129.
7. El Meziane,A., Lehtinen,S.K., Hance,N., Nijtmans,L.G., Dunbar,D., Holt,I.J. and Jacobs,H.T. (1998) A tRNA suppressor mutation in human mitochondria. Nature Genet, 18, 350-353.
8. Wittenhagen,L.M., Roy,M.D. and Kelley,S.O. (2003) The pathogenic U3271C human mitochondrial tRNA(Leu(UUR)) mutation disrupts a fragile anticodon stem. Nucleic Acids Res., 31, 596-601.
9. Wittenhagen,L.M. and Kelley,S.O. (2003) Impact of disease-related mitochondrial mutations on tRNA structure and function. Trends Biochem. Sci., 28, 605-611.
10. Sohm,B., Frugier,M., Brule,H., Olszak,K., Przykorska,A. and Florentz,C. (2003) Towards understanding human mitochondrial leucine aminoacylation identity. J. Mol. Biol, 328, 995-1010.
11. Toompuu,M., Yasukawa,T., Suzuki,T., Hakkinen,T., Spelbrink,J.N., Watanabe,K. and Jacobs,H.T. (2002) The 7472insC mitochondrial DNA mutation impairs the synthesis and extent of aminoacylation of tRNASer(UCN) but not its structure or rate of turnover. J. Biol. Chem., 277, 22240-22250.
12. Jaksch,M., Klopstock,T., Kurlemann,G., Dorner,M., Hofmann,S., Kleinle,S., Hegemann,S., Weissert,M., Muller-Hocker,J., Pongratz,D. et al. (1998) Progressive myoclonus epilepsy and mitochondrial myopathy associated with mutations in the tRNA(Ser(UCN)) gene. Ann. Neurol., 44, 635-640.
13. King,M.P. and Attardi,G. (1989) Human cells lacking mtDNA: Repopulation with exogenous mitochondria by complementation. Science, 246, 500-503.
14. Eubanks,J.H., Selleri,L., Hart,R., Rosette,C. and Evans,G.A. (1991) Isolation, localization, and physical mapping of a highly polymorphic locus on human chromosome 11q13. Genomics, 11, 720-729.
15. Rustin,P., Chretien,D., Bourgeron,T., Gerard,B., Rotig,A., Saudubray,J.M. and Munnich,A. (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin. Chim. Acta., 228, 35-51.
16. Sambrook,J., Fritsch,E.F. and Maniatis,T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, USA.
17. Yasukawa,T., Suzuki,T., Ishii,N., Ohta,S. and Watanabe,K. (2001) Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease. EMBO J., 20, 4794-4802.
18. Wilson,G.N., Hollar,B.A., Waterson,J.R. and Schmickel,R.D. (1978) Molecular analysis of cloned human 18S ribosomal DNA segments. Proc. Natl Acad. Sci. USA, 75, 5367-5371.
19. Fechter,P., Rudinger,J., Giege,R. and Theobald-Dietrich,A. (1998) Ribozyme processed tRNA transcripts with unfriendly internal promoter for T7 RNA polymerase: Production and activity. FEBS Lett., 436, 99-103.
20. Helm,M., Brule,H., Degoul,F., Cepanec,C., Leroux,J.P., Giege,R. and Florentz,C. (1998) The presence of modified nucleotides is required for cloverleaf folding of a human mitochondrial tRNA. Nucleic Acids Res., 26, 1636-1643.
21. Huang,Z. and Szostak,J.W. (1996) A simple method for 3′-labeling of RNA. Nucleic Acids Res., 24, 4360-4361.
22. Chomyn,A. (1996) In vivo labeling and analysis of human mitochondrial translation products. Methods Enzymol., 264, 197-211.
23. Laemmli,U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685.
24. Hofhaus,G., Shakeley,R.M. and Attardi,G. (1996) Use of polarography to detect respiration defects in cell cultures. Methods Enzymol., 264, 476-483.
25. Yokogawa,T., Watanabe,Y., Kumazawa,Y., Ueda,T., Hirao,I., Miura,K. and Watanabe,K. (1991) A novel cloverleaf structure found in mammalian mitochondrial tRNA(Ser) (UCN). Nucleic Acids Res., 19, 6101-6105.
26. Grafakou,O., Hol,F.A., Otfried,S.K., Siers,M.H., ter Laak,H., Trijbels,F., Ensenauer,R., Boelen,C. and Smeitink,J. (2003) Exercise intolerance, muscle pain and lactic acidaemia associated with a 7497G>A mutation in the tRNASer(UCN) gene. J. Inherit. Metab. Dis., 26, 593-600.
27. Bacman,S.R., Atencio,D.P. and Moraes,C.T. (2003) Decreased mitochondrial tRNALys steady-state levels and aminoacylation are associated with the pathogenic G8313A mitochondrial DNA mutation. Biochem. J., 374, 131-136.
28. McFarland,R., Clark,K.M., Morris,A.A., Taylor,R.W., Macphail,S., Lightowlers,R.N. and Turnbull,D.M. (2002) Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation. Nature Genet., 30, 145-146.
29. Toompuu,M., Tiranti,V., Zeviani,M. and Jacobs,H.T. (1999) Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids. Hum. Mol. Genet., 8, 2275-2283.
30. Toompuu,M., Levinger,L.L., Nadal,A., Gomez,J. and Jacobs,H.T. (2004) The 7472insC mtDNA mutation impairs 5′ and 3′ processing of tRNA(Ser(UCN)). Biochem. Biophys. Res. Commun., 322, 803-813.
31. Frank,D.N. and Pace,N.R. (1998) Ribonuclease P: Unity and diversity in a tRNA processing ribozyme. Annu. Rev. Biochem., 67, 153-180.
32. Christian,E.L., Zahler,N.H., Kaye,N.M. and Harris,M.E. (2002) Analysis of substrate recognition by the ribonucleoprotein endonuclease RNase P. Methods, 28, 307-322.
33. Bindoff,L.A., Howell,N., Poulton,J., McCullough,D.A., Morten,K.J., Lightowlers,R.N., Turnbull,D.M. and Weber,K. (1993) Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism. J. Biol. Chem., 268, 19559-19564.
34. Kaufmann,P., Koga,Y., Shanske,S., Hirano,M., DiMauro,S., King,M.P. and Schon,E.A. (1996) Mitochondrial DNA and RNA processing in MELAS. Ann. Neurol., 40, 172-180.
35. Koga,A., Koga,Y., Akita,Y., Fukiyama,R., Ueki,I., Yatsuga,S. and Matsuishi,T. (2003) Increased mitochondrial processing intermediates associated with three tRNA(Leu(UUR)) gene mutations. Neuromuscul. Disord., 13, 259-262.
36. Helm,M., Brule,H., Friede,D., Giege,R., Putz,D. and Florentz,C. (2000) Search for characteristic structural features of mammalian mitochondrial tRNAs. RNA, 6, 1356-1379.
37. Watanabe,Y., Kawai,G., Yokogawa,T., Hayashi,N., Kumazawa,Y., Ueda,T., Nishikawa,K., Hirao,I., Miura,K. and Watanabe,K. (1994) Higher-order structure of bovine mitochondrial tRNA(SerUGA): Chemical modification and computer modeling. Nucleic Acids Res., 22, 5378-5384.
38. Hayashi,I., Kawai,G. and Watanabe,K. (1998) Higher-order structure and thermal instability of bovine mitochondrial tRNASerUGA investigated by proton NMR spectroscopy. J. Mol. Biol., 284, 57-69.
39. Hao,R., Zhao,M.W., Hao,Z.X., Yao,Y.N. and Wang,E.D. (2005) A T-stem slip in human mitochondrial tRNALeu(CUN) governs its charging capacity. Nucleic Acids Res., 33, 3606-3613.
40. Friederich,M.W., Gast,F.U., Vacano,E. and Hagerman,P.J. (1995) Determination of the angle between the anticodon and aminoacyl acceptor stems of yeast phenylalanyl tRNA in solution. Proc. Natl Acad. Sci. USA, 92, 4803-4807.
41. Helm,M. and Attardi,G. (2004) Nuclear control of cloverleaf structure of human mitochondrial tRNA(Lys). J. Mol. Biol., 337, 545-560.
42. Ueda,T., Yotsumoto,Y., Ikeda,K. and Watanabe,K. (1992) The T-loop region of animal mitochondrial tRNA(Ser)(AGY) is a main recognition site for homologous seryl-tRNA synthetase. Nucleic Acids Res., 20, 2217-2222.
43. Shimada,N., Suzuki,T. and Watanabe,K. (2001) Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase. J. Biol. Chem., 276, 46770-46778.
44. Levinger,L., Morl,M. and Florentz,C. (2004) Mitochondrial tRNA 3′ end metabolism and human disease. Nucleic Acids Res., 32, 5430-5441.
45. Levinger,L., Oestreich,I., Florentz,C. and Morl,M. (2004) A pathogenesis-associated mutation in human mitochondrial tRNALeu(UUR) leads to reduced 3′ end processing and CCA addition. J. Mol. Biol., 337, 535-544.
46. Rossmanith,W. and Karwan,R.M. (1998) Impairment of tRNA processing by point mutations in mitochondrial tRNA(Leu)(UUR) associated with mitochondrial diseases. FEBS Lett., 433, 269-274.
47. Yasukawa,T., Suzuki,T., Ishii,N., Ueda,T., Ohta,S. and Watanabe,K. (2000) Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNA(Lys) with the MERRF encephalomyopathy pathogenic mutation. FEBS Lett., 467, 175-178.
48. Umeda,N., Suzuki,T., Yukawa,M., Ohya,Y., Shindo,H., Watanabe,K. and Suzuki,T. (2005) Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of the wobble base in mitochondrial tRNAs. Implications for the molecular pathogenesis of human mitochondrial diseases. J. Biol. Chem., 280, 1613-1624.
49. Schneider,A. (1996) Cytosolic yeast tRNA(His) is covalently modified when imported into mitochondria of Trypanosoma brucei. Nucleic Acids Res., 24, 1225-1228.