Sulfur Modifications of the Wobble U34 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(UUU)(Lys), tRNA(UUC)(Glu), and tRNA(UUG)(Gln), 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.