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.
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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 -