thiouridine and 5-taurinomethyluridine

Mitochondria are eukaryotic organelles that generate most of the energy in the cell by oxidative phosphorylation (OXPHOS). Each mitochondrion contains multiple copies of a closed circular double-stranded DNA genome (mtDNA). Human (mammalian) mtDNA encodes 13 essential subunits of the inner membrane complex responsible for OXPHOS. These mRNAs are translated by the mitochondrial protein synthesis machinery, which uses the 22 species of mitochondrial tRNAs (mt tRNAs) encoded by mtDNA. The unique structural features of mt tRNAs distinguish them from cytoplasmic tRNAs bearing the canonical cloverleaf structure. The genes encoding mt tRNAs are highly susceptible to point mutations, which are a primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. A large number of nuclear factors involved in the biogenesis and function of mt tRNAs have been identified and characterized, including processing endonucleases, tRNA-modifying enzymes, and aminoacyl-tRNA synthetases. These nuclear factors are also targets of pathogenic mutations linked to various diseases, indicating the functional importance of mt tRNAs for mitochondrial activity.

Topics: Amino Acyl-tRNA Synthetases; Aminoacylation; Animals; Humans; Mammals; MELAS Syndrome; Mitochondria; Mitochondrial Diseases; Mutation; Oxidative Phosphorylation; Protein Conformation; RNA; RNA Processing, Post-Transcriptional; RNA, Mitochondrial; RNA, Transfer; Thiouridine; Transcription, Genetic; Uridine

Unique taurine-containing uridine derivatives, 5-taurinomethyluridine (tau m5U) and 5-taurinomethyl-2-thiouridine (tau m5s2U), which were discovered in mammalian mitochondrial tRNAs, exist at the first position of the anticodon. In this paper, we report the first efficient synthesis of tau m5U and tau m5s2U and describe their physicochemical properties. These modified ribonucleosides were synthesized by the reaction of 5-substituted uridine derivatives with a tetrabutylammonium salt of taurine that is highly reactive and well-soluble in common organic solvents. UV and 1H NMR spectrometric studies revealed the structural properties of the taurine-containing base moieties and the sugar conformations of these modified ribonucleosides.

Topics: Molecular Structure; Spectrum Analysis; Taurine; Thiouridine; Uridine

Recently, novel base-modified uridine derivatives, 5-taurinomethyluridine (tau m(5)U) and 5-taurinomethyl-2-thiouridine (tau m(5)s(2)U) have been discovered from mammalian mitochondrial tRNAs, and these modified ribonucleosides were found to exist at the first position of the anticodon. We herein report efficient reactions for the synthesis of RNA oligomers including these base-modified ribonucleosides.

Topics: Amides; Oligoribonucleotides; Phosphoric Acids; RNA; Thiouridine; Uridine