Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

Takehiro Yasukawa, Tsutomu Suzuki, Takeo Suzuki, Takuya Ueda, Shigeo Ohta, Kimitsuna Watanabe

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

The mitochondrial tRNA(Leu)(UUR) (R=A or G) gene possesses several hot spots for pathogenic mutations. A point mutation at nucleotide position 3243 or 3271 is associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes and maternally inherited diabetes with deafness. Detailed studies on two tRNAs(Leu)(UUR) with the 3243 or 3271 mutation revealed some common characteristics in cybrid cells: (i) a decreased life span, resulting in a 70% decrease in the amounts of the tRNAs in the steady state, (ii) a slight decrease in the ratios of aminoacyl- tRNAs(Leu)(UUR) versus uncharged tRNAs(Leu)(UUR), and (iii) accurate aminoacylation with leucine without any misacylation. As a marked result, both of the mutant tRNA molecules were deficient in a modification of uridine that occurs in the normal tRNA(Leu)(UUR) at the first position of the anticodon. The lack of this modification may lead to the mistranslation of leucine into non-cognate phenylalanine codons by mutant tRNAs(Leu)(UUR), according to the mitochondrial wobble rule, and/or a decrease in the rate of mitochondrial protein synthesis. This finding could explain why two different mutations (3243 and 3271) manifest indistinguishable clinical features.

Original languageEnglish
Pages (from-to)4251-4257
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number6
DOIs
Publication statusPublished - Feb 11 2000

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RNA, Transfer, Leu
MELAS Syndrome
Anticodon
Nucleotides
Defects
Mutation
Transfer RNA
Leucine
Aminoacylation
Uridine
Mitochondrial Proteins
Medical problems
Phenylalanine
Point Mutation
Codon
Milk
Genes
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. / Yasukawa, Takehiro; Suzuki, Tsutomu; Suzuki, Takeo; Ueda, Takuya; Ohta, Shigeo; Watanabe, Kimitsuna.

In: Journal of Biological Chemistry, Vol. 275, No. 6, 11.02.2000, p. 4251-4257.

Research output: Contribution to journalArticle

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