The pathogenic A4269G mutation in human mitochondrial tRNA Ile alters the T-stem structure and decreases the binding affinity for elongation factor Tu

Narumi Hino, Tsutomu Suzuki, Takehiro Yasukawa, Kohji Seio, Kimitsuna Watanabe, Takuya Ueda

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The A4269G mutation in the human mitochondrial (mt) tRNAIle gene is associated with fatal cardiomyopathy. This mutation completely inhibits protein synthesis in mitochondria, thereby significantly reducing their respiratory activity.The steady-state amount of tRNAIle in cells bearing the A4269G mutation is almost half that of control cells. We previously reported that this mutation causes tRNAIle to be unstable both in vivo and in vitro. To investigate whether the instability of the mutant tRNAIle is due to structural alterations, a nuclease-probing experiment was performed with a mitochondrial enzymatic extract, which showed that the A4269G mutation destabilizes the T-stem of the mutant tRNAIle. In addition, measurements of the binding affinity of the aminoacylated mutant tRNAIle for mt elongation factor Tu (EF-Tu) showed that the mutant tRNAIle binds mt EF-Tu less efficiently than the wild-type does. This observation provides insight into the molecular pathology associated with tRNA dysfunction caused by this pathogenic point mutation.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalGenes to Cells
Volume9
Issue number3
DOIs
Publication statusPublished - 2004 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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