Abstract
Pathogenic point mutations in mitochondrial tRNA genes are known to cause a variety of human mitochondrial diseases. Reports have associated an A4317G mutation in the mitochondrial tRNAIle gene with fatal infantile cardiomyopathy and an A10044G mutation in the mitochondrial tRNAGly gene with sudden infant death syndrome. Here we demonstrate that both mutations inhibit in vitro CCA-addition to the respective tRNA by the human mitochondrial CCA-adding enzyme. Structures of these two mutant tRNAs were examined by nuclease probing. In the case of the A4317G tRNAIle mutant, structural rearrangement of the T-arm region, conferring an aberrantly stable T-arm structure and an increased Tm value, was clearly observed. In the case of the A10044G tRNAGly mutant, high nuclease sensitivity in both the T- and D-loops suggested a weakened interaction between the loops. These are the first reported instances of inefficient CCA-addition being one of the apparent molecular pathogeneses caused by pathogenic point mutations in human mitochondrial tRNA genes.
| Original language | English |
|---|---|
| Pages (from-to) | 16828-16833 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 278 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 2003 May 9 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Decreased CCA-addition in human mitochondrial tRNAs bearing a pathogenic A4317G or A10044G mutation. / Tomari, Yukihide; Hino, Narumi; Nagaike, Takashi; Suzuki, Tsutomu; Ueda, Takuya.
In: Journal of Biological Chemistry, Vol. 278, No. 19, 09.05.2003, p. 16828-16833.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Decreased CCA-addition in human mitochondrial tRNAs bearing a pathogenic A4317G or A10044G mutation
AU - Tomari, Yukihide
AU - Hino, Narumi
AU - Nagaike, Takashi
AU - Suzuki, Tsutomu
AU - Ueda, Takuya
PY - 2003/5/9
Y1 - 2003/5/9
N2 - Pathogenic point mutations in mitochondrial tRNA genes are known to cause a variety of human mitochondrial diseases. Reports have associated an A4317G mutation in the mitochondrial tRNAIle gene with fatal infantile cardiomyopathy and an A10044G mutation in the mitochondrial tRNAGly gene with sudden infant death syndrome. Here we demonstrate that both mutations inhibit in vitro CCA-addition to the respective tRNA by the human mitochondrial CCA-adding enzyme. Structures of these two mutant tRNAs were examined by nuclease probing. In the case of the A4317G tRNAIle mutant, structural rearrangement of the T-arm region, conferring an aberrantly stable T-arm structure and an increased Tm value, was clearly observed. In the case of the A10044G tRNAGly mutant, high nuclease sensitivity in both the T- and D-loops suggested a weakened interaction between the loops. These are the first reported instances of inefficient CCA-addition being one of the apparent molecular pathogeneses caused by pathogenic point mutations in human mitochondrial tRNA genes.
AB - Pathogenic point mutations in mitochondrial tRNA genes are known to cause a variety of human mitochondrial diseases. Reports have associated an A4317G mutation in the mitochondrial tRNAIle gene with fatal infantile cardiomyopathy and an A10044G mutation in the mitochondrial tRNAGly gene with sudden infant death syndrome. Here we demonstrate that both mutations inhibit in vitro CCA-addition to the respective tRNA by the human mitochondrial CCA-adding enzyme. Structures of these two mutant tRNAs were examined by nuclease probing. In the case of the A4317G tRNAIle mutant, structural rearrangement of the T-arm region, conferring an aberrantly stable T-arm structure and an increased Tm value, was clearly observed. In the case of the A10044G tRNAGly mutant, high nuclease sensitivity in both the T- and D-loops suggested a weakened interaction between the loops. These are the first reported instances of inefficient CCA-addition being one of the apparent molecular pathogeneses caused by pathogenic point mutations in human mitochondrial tRNA genes.
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U2 - 10.1074/jbc.M213216200
DO - 10.1074/jbc.M213216200
M3 - Article
VL - 278
SP - 16828
EP - 16833
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -