Sulfur Modifications of the Wobble U(34) in tRNAs and their Intracellular Localization in Eukaryotic Cells

The wobble uridine (U(34)) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNA(Lys)(UUU), tRNA(Glu)(UUC), and tRNA(Gln)(UUG), harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U(34), respectively. Both modifications are necessary to construct the proper anticodon loop structure and to enable them to exert their functions in translation. Thio-modification of U(34) (s(2)U(34)) is found in both cytosolic tRNAs (cy-tRNAs) and mitochondrial tRNAs (mt-tRNAs). Although l-cysteine desulfurase is required in both cases, subsequent sulfur transfer pathways to cy-tRNAs and mt-tRNAs are different due to their distinct intracellular locations. The s(2)U(34) formation in cy-tRNAs involves a sulfur delivery system required for the biosynthesis of iron-sulfur (Fe/S) clusters and certain resultant Fe/S proteins. This review addresses presumed sulfur delivery pathways for the s(2)U(34) formation in distinct intracellular locations, especially that for cy-tRNAs in comparison with that for mt-tRNAs.