{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:38:01Z","timestamp":1791340681698,"version":"4.3.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,10,19]]},"abstract":"<jats:p>\n                    Point mutations in the mitochondrial (mt) tRNA\n                    <jats:sup>Leu(UUR)<\/jats:sup>\n                    gene are responsible for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a subgroup of mitochondrial encephalomyopathic diseases. We previously showed that mt tRNA\n                    <jats:sup>Leu(UUR)<\/jats:sup>\n                    with an A3243G or T3271C mutation derived from patients with MELAS are deficient in a normal taurine-containing modification (\u03c4m\n                    <jats:sup>5<\/jats:sup>\n                    U; 5-taurinomethyluridine) at the anticodon wobble position. To examine decoding disorder of the mutant tRNA due to the wobble modification deficiency independent of the pathogenic point mutation itself, we used a molecular surgery technique to construct an mt tRNA\n                    <jats:sup>Leu(UUR)<\/jats:sup>\n                    molecule lacking the taurine modification but without the pathogenic mutation. This \u201coperated\u201d mt tRNA\n                    <jats:sup>Leu(UUR)<\/jats:sup>\n                    without the taurine modification showed severely reduced UUG translation but no decrease in UUA translation. We thus concluded that the UUG codon\u2013specific translational defect of the mutant mt tRNAs\n                    <jats:sup>Leu(UUR)<\/jats:sup>\n                    is the primary cause of MELAS at the molecular level. This result could explain the complex I deficiency observed clinically in MELAS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0405173101","type":"journal-article","created":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T20:24:32Z","timestamp":1097526272000},"page":"15070-15075","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":264,"title":["Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease"],"prefix":"10.1073","volume":"101","author":[{"given":"Yohei","family":"Kirino","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaisuke","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitsuna","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kanagawa 211-8533, Japan; and Department of Obstetrics and Gynecology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, and Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; 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