The 7472insC mitochondrial DNA mutation impairs the synthesis and extent of aminoacylation of tRNASer(UCN) but not its structure or rate of turnover

Marina Toompuu, Takehiro Yasukawa, Tsutomu Suzuki, Terhi Hakkinen, Johannes N. Spelbrink, Kimitsuna Watanabe, Howard T. Jacobs

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46 Citations (Scopus)


The 7472insC mitochondrial DNA mutation in the tRNASer(UCN) gene is associated with sensorineural deafness combined, in some patients, with a wider neurological syndrome. In cultured cybrid cells it causes a 70% decrease in tRNASer(UCN) abundance and mild respiratory impairment, previously suggested to be due to decreased tRNA stability. When mitochondrial transcription was blocked by ethidium bromide treatment, the half-life of the mutant tRNA was not significantly different from that of wild-type tRNASer(UCN). Over-expression of mitochondrial translational elongation factor EF-Tu also had no effect on the mutant phenotype. However, during recovery from prolonged ethidium bromide treatment, the synthesis of the mutant tRNASer(UCN) was specifically impaired, without polarity effects on downstream tRNAs of the light strand transcription unit. We infer that the mutation acts posttranscriptionally to decrease tRNASer(UCN) abundance by affecting its synthesis rather than its stability. The extent of aminoacylation of the mutant tRNA was also decreased by ∼25%. In contrast, the mutation had no detectable effect on tRNASer(UCN) base modification or structure other than the insertion of an extra guanosine templated by the mutation, which was structurally protected from nuclease digestion like the surrounding nucleotides. These findings indicate a common molecular process underlying sensorineural deafness caused by mitochondrial tRNASer(UCN) mutations.

Original languageEnglish
Pages (from-to)22240-22250
Number of pages11
JournalJournal of Biological Chemistry
Issue number25
Publication statusPublished - Jun 21 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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