Mitochondria-specific RNA-modifying Enzymes Responsible for the Biosynthesis of the Wobble Base in Mitochondrial tRNAs
Journal of Biological Chemistry Volume 280 Issue 2
Page 1613-1624
published_at 2005-01-14
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| File | |
| Title ( eng ) |
Mitochondria-specific RNA-modifying Enzymes Responsible for the Biosynthesis of the Wobble Base in Mitochondrial tRNAs
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| Creator |
Umeda Noriko
Suzuki Takeo
Ohya Yoshikazu
Shindo Heisaburo
Watanabe Kimitsuna
Suzuki Tsutomu
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| Source Title |
Journal of Biological Chemistry
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| Volume | 280 |
| Issue | 2 |
| Start Page | 1613 |
| End Page | 1624 |
| Abstract |
Human mitochondrial (mt) tRNALys has a taurine-containing modified uridine, 5-taurinomethyl-2-thiouridine (τm5s2U), at its anticodon wobble position. We previously found that the mt tRNALys, carrying the A8344G mutation from cells of patients with myoclonus epilepsy associated with ragged-red fibers (MERRF), lacks the τm5s2U modification. Here we describe the identification and characterization of a tRNA-modifying enzyme MTU1 (mitochondrial tRNA-specific 2-thiouridylase 1) that is responsible for the 2-thiolation of the wobble position in human and yeast mt tRNAs. Disruption of the yeast MTU1 gene eliminated the 2-thio modification of mt tRNAs and impaired mitochondrial protein synthesis, which led to reduced respiratory activity. Furthermore, when MTO1 or MSS1, which are responsible for the C5 substituent of the modified uridine, was disrupted along with MTU1, a much more severe reduction in mitochondrial activity was observed. Thus, the C5 and 2-thio modifications act synergistically in promoting efficient cognate codon decoding. Partial inactivation of MTU1 in HeLa cells by small interference RNA also reduced their oxygen consumption and resulted in mitochondria with defective membrane potentials, which are similar phenotypic features observed in MERRF.
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| Descriptions |
This work was supported by grants-in-aid for scientific research on priority areas from the Ministry of Education, Science, Sports, and Culture of Japan, and by a grant from the New Energy and Industrial Technology Development Organization (to T. S.).
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| Language |
eng
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| Resource Type | journal article |
| Publisher |
The American Society for Biochemistry and Molecular Biology, Inc.
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| Date of Issued | 2005-01-14 |
| Rights |
This research was originally published in the Journal of Biological Chemistry. Noriko Umeda, Takeo Suzuki, Masashi Yukawa, Yoshikazu Ohya, Heisaburo Shindo, Kimitsuna Watanabe, and Tsutomu Suzuki. Mitochondria-specific RNA-modifying Enzymes Responsible for the Biosynthesis of the Wobble Base in Mitochondrial tRNAs. J Biol Chem. 2005; 280:1613-1624. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
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| Publish Type | Version of Record |
| Access Rights | open access |
| Source Identifier |
[ISSN] 0021-9258
[ISSN] 1083-351X
[DOI] 10.1074/jbc.M409306200
[DOI] https://doi.org/10.1074/jbc.M409306200
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