Reduction of mitochondrial tRNA Leu(UUR) aminoacylation by some MELAS-associated mutations

Rui Hao; Yong Neng Yao; Yong Gang Zheng; Min Gang Xu; En Duo Wang

doi:10.1016/j.febslet.2004.11.004

Reduction of mitochondrial tRNA ^Leu(UUR) aminoacylation by some MELAS-associated mutations

Rui Hao, Yong Neng Yao, Yong Gang Zheng, Min Gang Xu, En Duo Wang

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA. Five single nucleotide substitutions within the human mitochondrial tRNA ^Leu(UUR) gene have been reported to be associated with MELAS. Here, we provide in vitro evidence that the aminoacylation capacities of these five hmtRNA ^Leu(UUR) transcripts are reduced to different extents relative to the wild-type hmtRNA ^Leu(UUR) transcript. A thermal denaturation experiment showed that the A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild-type hmtRNA ^Leu(UUR), indicating that it may act as an inhibitor in the mitochondrial heteroplasmic environment.

Original language	English
Pages (from-to)	135-139
Number of pages	5
Journal	FEBS Letters
Volume	578
Issue number	1-2
DOIs	https://doi.org/10.1016/j.febslet.2004.11.004
State	Published - 3 Dec 2004
Externally published	Yes

Keywords

Aminoacylation
Human mitochondrion
MELAS-related mutation
tRNA (UUR)

Access to Document

10.1016/j.febslet.2004.11.004

Cite this

@article{0c226990615742be8fe9631549b9007a,

title = "Reduction of mitochondrial tRNA Leu(UUR) aminoacylation by some MELAS-associated mutations",

abstract = "The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA. Five single nucleotide substitutions within the human mitochondrial tRNA Leu(UUR) gene have been reported to be associated with MELAS. Here, we provide in vitro evidence that the aminoacylation capacities of these five hmtRNA Leu(UUR) transcripts are reduced to different extents relative to the wild-type hmtRNA Leu(UUR) transcript. A thermal denaturation experiment showed that the A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild-type hmtRNA Leu(UUR), indicating that it may act as an inhibitor in the mitochondrial heteroplasmic environment.",

keywords = "Aminoacylation, Human mitochondrion, MELAS-related mutation, tRNA (UUR)",

author = "Rui Hao and Yao, {Yong Neng} and Zheng, {Yong Gang} and Xu, {Min Gang} and Wang, {En Duo}",

note = "Funding Information: This work was funded by the Chinese Natural Sciences Foundation (Grant 30330180), the Chinese Academy of Sciences (Grant KSCX2-2-04), the 863 projects of China (Grant 2004AA235091), and the Shanghai Committee of Science and Technology (Grant number 02DJ140567).",

year = "2004",

month = dec,

day = "3",

doi = "10.1016/j.febslet.2004.11.004",

language = "English",

volume = "578",

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journal = "FEBS Letters",

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T1 - Reduction of mitochondrial tRNA Leu(UUR) aminoacylation by some MELAS-associated mutations

AU - Hao, Rui

AU - Yao, Yong Neng

AU - Zheng, Yong Gang

AU - Xu, Min Gang

AU - Wang, En Duo

N1 - Funding Information: This work was funded by the Chinese Natural Sciences Foundation (Grant 30330180), the Chinese Academy of Sciences (Grant KSCX2-2-04), the 863 projects of China (Grant 2004AA235091), and the Shanghai Committee of Science and Technology (Grant number 02DJ140567).

PY - 2004/12/3

Y1 - 2004/12/3

N2 - The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA. Five single nucleotide substitutions within the human mitochondrial tRNA Leu(UUR) gene have been reported to be associated with MELAS. Here, we provide in vitro evidence that the aminoacylation capacities of these five hmtRNA Leu(UUR) transcripts are reduced to different extents relative to the wild-type hmtRNA Leu(UUR) transcript. A thermal denaturation experiment showed that the A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild-type hmtRNA Leu(UUR), indicating that it may act as an inhibitor in the mitochondrial heteroplasmic environment.

AB - The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA. Five single nucleotide substitutions within the human mitochondrial tRNA Leu(UUR) gene have been reported to be associated with MELAS. Here, we provide in vitro evidence that the aminoacylation capacities of these five hmtRNA Leu(UUR) transcripts are reduced to different extents relative to the wild-type hmtRNA Leu(UUR) transcript. A thermal denaturation experiment showed that the A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild-type hmtRNA Leu(UUR), indicating that it may act as an inhibitor in the mitochondrial heteroplasmic environment.

KW - Aminoacylation

KW - Human mitochondrion

KW - MELAS-related mutation

KW - tRNA (UUR)

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