Role of Modified Nucleosides in the Translation Function of tRNAs from Extreme Thermophilic Bacteria and Animal Mitochondria

• Watanabe Kimitsuna

  Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo

抄録

This report characterizes the structure and function of four modified nucleosides first identified by myself or members of my research group in thermophilic bacteria and animal mitochondria over the past 30 years. I identified 2-thioribothymidine (s²T) (or 5-methyl-2-thiouridine (m⁵s²U)) in 1974 at position 54 in the T loop of tRNAs from an extreme thermophile, Thermus thermophilus, as well as related thermophiles, and a good deal of evidence has shown that it is required for thermostabilization of tRNAs, functioning at high temperatures. The functional roles and the biosynthetic pathway of s²T are outlined here. My research group has identified three novel modified nucleosides, 5-formylcytidine (f⁵C), N-(uridine-5-ylmethyl)taurine (τm⁵U), and N-(2-thiouridine-5-ylmethyl)taurine (τm⁵s²U), at the first anticodon position of mitochondrial (mt) tRNAs from higher animals (f⁵C is present in tRNA^Met, τm⁵U in tRNA^Leu(UUR) and tRNA^Trp, and τm⁵s²U in tRNA^Gln, tRNA^Lys, and tRNA^Glu). Their chemical structures were determined and their functional roles in translation were examined. Additionally, f⁵C at the first anticodon position of mt tRNA^Met plays a crucial role in decoding the AUA codon (decoded as isoleucine in the universal genetic code system) as methionine, which will form the second topic of this article. Defective modification of τm⁵U and τm⁵s²U at the first anticodon position in human mt tRNA^Leu(UUR) and tRNA^Lys, respectively, is the result of point mutations in these tRNAs in mitochondria. It is strongly suggested that these defects are the direct cause of two mitochondrial diseases, MELAS (mitochondrial encephalomyopathies, encephalopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonus epilepsy associated with ragged-red fibers). Their molecular mechanisms are also discussed here. These studies would serve to highlight again the importance of modified tRNA nucleosides in the structure and function of tRNAs.

収録刊行物

• Bulletin of the Chemical Society of Japan

  Bulletin of the Chemical Society of Japan 80 (7), 1253-1267, 2007

  公益社団法人 日本化学会

キーワード

• General Chemistry

詳細情報

• CRID: 1390001204144463360
• NII論文ID: 130004152364
• DOI: 10.1246/bcsj.80.1253
• ISSN: 13480634
• ISSN: 00092673
• Web Site: https://academic.oup.com/bcsj/article-pdf/80/7/1253/56268308/bcsj.80.1253.pdf
• 本文言語コード: en
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