tRNA Sec is initially charged with
Selenocysteine biosynthesis uniquely occurs on its tRNA scaffold because free selenocysteine is unstable and oxidized spontaneously. Initial aminoacylation attaches serine, since no amino acid pool provides selenocysteine directly. Seryl-tRNA synthetase SerRS recognizes tRNASec despite unusual structure, esterifying serine to terminal A76 2' hydroxyl. This serine adduct provides hydroxyl substrate for subsequent phosphorylation reaction and replacement by selenophosphate donor. Maintaining amino acid covalently attached to tRNA throughout conversion avoids release of reactive intermediate, channels toxic selenium safely into protein, and ensures only tRNASec-dependent proteins undergo modification, preserving specificity across translation apparatus.
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 5: tRNASec Aminoacylation with Serine