A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile)

Takehiro Yasukawa, Narumi Hino, Tsutomu Suzuki, Kimitsuna Watanabe, Takuya Ueda, Shigeo Ohta

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNA(Leu) (UUR) and tRNA(Lys) genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNA(Ile) with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNA(Ile) reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNA(Ile) both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNA(Ile) itself is intrinsically unstable.

Original languageEnglish
Pages (from-to)3779-3784
Number of pages6
JournalNucleic acids research
Volume28
Issue number19
Publication statusPublished - 2000 Oct 1
Externally publishedYes

Fingerprint

RNA, Transfer, Ile
Transfer RNA
Point Mutation
Nucleotides
RNA, Transfer, Lys
Mitochondrial Encephalomyopathies
RNA, Transfer, Leu
Anticodon
Mitochondrial Genes
Freezing
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Yasukawa, T., Hino, N., Suzuki, T., Watanabe, K., Ueda, T., & Ohta, S. (2000). A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile). Nucleic acids research, 28(19), 3779-3784.

A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile). / Yasukawa, Takehiro; Hino, Narumi; Suzuki, Tsutomu; Watanabe, Kimitsuna; Ueda, Takuya; Ohta, Shigeo.

In: Nucleic acids research, Vol. 28, No. 19, 01.10.2000, p. 3779-3784.

Research output: Contribution to journalArticle

Yasukawa, T, Hino, N, Suzuki, T, Watanabe, K, Ueda, T & Ohta, S 2000, 'A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile)', Nucleic acids research, vol. 28, no. 19, pp. 3779-3784.
Yasukawa T, Hino N, Suzuki T, Watanabe K, Ueda T, Ohta S. A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile). Nucleic acids research. 2000 Oct 1;28(19):3779-3784.
Yasukawa, Takehiro ; Hino, Narumi ; Suzuki, Tsutomu ; Watanabe, Kimitsuna ; Ueda, Takuya ; Ohta, Shigeo. / A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile). In: Nucleic acids research. 2000 ; Vol. 28, No. 19. pp. 3779-3784.
@article{8e03139d0bfb438da6b7bc05581d62a0,
title = "A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile)",
abstract = "Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNA(Leu) (UUR) and tRNA(Lys) genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNA(Ile) with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNA(Ile) reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNA(Ile) both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNA(Ile) itself is intrinsically unstable.",
author = "Takehiro Yasukawa and Narumi Hino and Tsutomu Suzuki and Kimitsuna Watanabe and Takuya Ueda and Shigeo Ohta",
year = "2000",
month = "10",
day = "1",
language = "English",
volume = "28",
pages = "3779--3784",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "19",

}

TY - JOUR

T1 - A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile)

AU - Yasukawa, Takehiro

AU - Hino, Narumi

AU - Suzuki, Tsutomu

AU - Watanabe, Kimitsuna

AU - Ueda, Takuya

AU - Ohta, Shigeo

PY - 2000/10/1

Y1 - 2000/10/1

N2 - Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNA(Leu) (UUR) and tRNA(Lys) genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNA(Ile) with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNA(Ile) reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNA(Ile) both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNA(Ile) itself is intrinsically unstable.

AB - Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNA(Leu) (UUR) and tRNA(Lys) genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNA(Ile) with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNA(Ile) reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNA(Ile) both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNA(Ile) itself is intrinsically unstable.

UR - http://www.scopus.com/inward/record.url?scp=0034307731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034307731&partnerID=8YFLogxK

M3 - Article

C2 - 11000270

AN - SCOPUS:0034307731

VL - 28

SP - 3779

EP - 3784

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 19

ER -