Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations

Takehiro Yasukawa; Tsutomu Suzuki; Shigeo Ohta; Kimitsuna Watanabe

doi:10.1016/S1567-7249(02)00033-8

Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations

Takehiro Yasukawa
, Tsutomu Suzuki
, Shigeo Ohta
, Kimitsuna Watanabe

Research output: Contribution to journal › Review article › peer-review

15 Citations (Scopus)

Abstract

By purifying mutant mitochondrial tRNAs, we were able to ascertain that post-transcriptional modification at the anticodon wobble uridine is absent in tRNA^Lys with the 8344 MERRF mutation and in tRNA^Leu(UUR) with either the 3243 or 3271 MELAS mutation. Both the MERRF and MELAS mutant tRNAs substantially lost their translational ability, the extent of the loss in each mutant corresponding to the reduction in actual mitochondrial translational activity. Lack of the wobble modification deprived mutant tRNA^Lys of interaction with the cognate codons. These features indicate that the modification defect plays a primary role in the molecular pathophysiology of these mitochondrial diseases.

Original language	English
Pages (from-to)	129-141
Number of pages	13
Journal	Mitochondrion
Volume	2
Issue number	1-2
DOIs	https://doi.org/10.1016/S1567-7249(02)00033-8
Publication status	Published - Nov 2002
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Medicine
Molecular Biology
Cell Biology

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10.1016/S1567-7249(02)00033-8

Cite this

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title = "Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations",

abstract = "By purifying mutant mitochondrial tRNAs, we were able to ascertain that post-transcriptional modification at the anticodon wobble uridine is absent in tRNALys with the 8344 MERRF mutation and in tRNALeu(UUR) with either the 3243 or 3271 MELAS mutation. Both the MERRF and MELAS mutant tRNAs substantially lost their translational ability, the extent of the loss in each mutant corresponding to the reduction in actual mitochondrial translational activity. Lack of the wobble modification deprived mutant tRNALys of interaction with the cognate codons. These features indicate that the modification defect plays a primary role in the molecular pathophysiology of these mitochondrial diseases.",

keywords = "Anticodon, Mitochondrial disease, Mitochondrial tRNA, Mitochondrial translation, Post-transcriptional modification",

author = "Takehiro Yasukawa and Tsutomu Suzuki and Shigeo Ohta and Kimitsuna Watanabe",

note = "Funding Information: We would like to express our thanks to Dr J.-I. Hayashi (Tsukuba University) for giving us an original mutant cybrid cell line of the ME1-4 clone and to Dr L.L. Spremulli (University of North Carolina) for kindly providing an EF-Tu mt expression vector. We are also grateful to Dr Norie Ishii (Nippon Medical School), Dr T. Hanada (Tokyo University), and Mr T. Suzuki (Tokyo University) for their technical assistance and helpful advice. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (Japan).",

year = "2002",

month = nov,

doi = "10.1016/S1567-7249(02)00033-8",

language = "English",

volume = "2",

pages = "129--141",

journal = "Mitochondrion",

issn = "1567-7249",

publisher = "Elsevier B.V.",

number = "1-2",

}

TY - JOUR

T1 - Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations

AU - Yasukawa, Takehiro

AU - Suzuki, Tsutomu

AU - Ohta, Shigeo

AU - Watanabe, Kimitsuna

N1 - Funding Information: We would like to express our thanks to Dr J.-I. Hayashi (Tsukuba University) for giving us an original mutant cybrid cell line of the ME1-4 clone and to Dr L.L. Spremulli (University of North Carolina) for kindly providing an EF-Tu mt expression vector. We are also grateful to Dr Norie Ishii (Nippon Medical School), Dr T. Hanada (Tokyo University), and Mr T. Suzuki (Tokyo University) for their technical assistance and helpful advice. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (Japan).

PY - 2002/11

Y1 - 2002/11

N2 - By purifying mutant mitochondrial tRNAs, we were able to ascertain that post-transcriptional modification at the anticodon wobble uridine is absent in tRNALys with the 8344 MERRF mutation and in tRNALeu(UUR) with either the 3243 or 3271 MELAS mutation. Both the MERRF and MELAS mutant tRNAs substantially lost their translational ability, the extent of the loss in each mutant corresponding to the reduction in actual mitochondrial translational activity. Lack of the wobble modification deprived mutant tRNALys of interaction with the cognate codons. These features indicate that the modification defect plays a primary role in the molecular pathophysiology of these mitochondrial diseases.

AB - By purifying mutant mitochondrial tRNAs, we were able to ascertain that post-transcriptional modification at the anticodon wobble uridine is absent in tRNALys with the 8344 MERRF mutation and in tRNALeu(UUR) with either the 3243 or 3271 MELAS mutation. Both the MERRF and MELAS mutant tRNAs substantially lost their translational ability, the extent of the loss in each mutant corresponding to the reduction in actual mitochondrial translational activity. Lack of the wobble modification deprived mutant tRNALys of interaction with the cognate codons. These features indicate that the modification defect plays a primary role in the molecular pathophysiology of these mitochondrial diseases.

KW - Anticodon

KW - Mitochondrial disease

KW - Mitochondrial tRNA

KW - Mitochondrial translation

KW - Post-transcriptional modification

UR - https://www.scopus.com/pages/publications/0036838879

UR - https://www.scopus.com/pages/publications/0036838879#tab=citedBy

U2 - 10.1016/S1567-7249(02)00033-8

DO - 10.1016/S1567-7249(02)00033-8

M3 - Review article

C2 - 16120315

AN - SCOPUS:0036838879

SN - 1567-7249

VL - 2

SP - 129

EP - 141

JO - Mitochondrion

JF - Mitochondrion

IS - 1-2

ER -

Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations

Abstract

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