| Research Abstract |
Taurine (2-aminoethanesulphonic acid), a naturally occurring, sulfur-containing amino acid, is found at high concentrations in mammalian plasma and tissues, and is often used as an ingredient of nutritional supplements. In humans, taurine is known to be involved in a variety of important processes, including synthesis of bile salts, modulation of calcium fluxes, maintenance of photoreceptor cells, modulation of neuronal excitability, antioxidation, osmoregulation, and cell proliferation. However, taurine has not thus far been found as a component of a protein or a nucleic acid, and its precise biochemical functions are still not fully understood. In this study, we report the identification of two novel modified uridines in human (and bovine) mitochondrial tRNAs that possess a sulfonic acid group derived from taurine : 5-taurinomethyluridine and 5-taurinomethyl-2-thiouridine. Experimental findings revealed that these taurine-containing uridines were synthesized by the direct incorporati
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on of taurine supplied to the medium. This is the first reported evidence that taurine is a constituent of biological macromolecules, unveiling the prospect of obtaining new insights into the functions of this abundant amino acid. Further, we recently found a deficiency in the normal modification of these newly found taurine-containing uridines at the wobble position of mitochondrial tRNA^<Leu> and tRNA^<Lys> obtained from human pathogenic cells of the mitochondrial encephalomyopathies MELAS [JBC, 275, 425 1-4257 (2000)] and MERRF [FEBS, 467, 175-1 78 (2000)], respectively. We have also proposed that a decoding disorder arising from this modification defect is likely to be one of the main causes of mitochondrial dysfunction [EMBO, 20, 4794-4802 (200 1)]. Since the chemical structures of these modified uridines and their biosynthetic pathways has been revealed in this study, we have opened the door to understanding the pathogenesis of associated mitochondrial diseases and to the investigation of possible therapies. Less
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