Selenocysteine tRNA[Ser]Sec Isoacceptors as Central Components in Selenoprotein Biosynthesis in Eukaryotes

In recent years, a variety of experimental results have led to the surprising conclusion that under certain circumstances the UGA termination codon signals the translational insertion of selenocysteine into protein. These studies include the demonstration that (1) a TGA codon (that corresponds to a selenocysteine moiety in the resulting gene products [Cone et al., 1976; Gunzler et al., 1984]) occurs in the open reading frame of genes for formate dehydrogenase in E. coli (Zinoni et al., 1986) and glutathione peroxidase (GPx) in mammals (Chambers et al., 1986; Sukenaga et al., 1987; Mullenbach et al., 1988) and (2) a selenocysteyl-tRNA that decodes UGA occurs in E. coli (Leinfelder et al., 1989) and mammals (Lee et al., 1989b). The genes that utilize UGA for selenocysteine (for review see Stadtman, 1991) and the tRNAs that serve as carrier molecules for the biosynthesis of selenocysteine and donate selenocysteine to protein have been observed in a wide variety of organisms as described below. This phenomenon has evolved in all life kingdoms and thus the universal genetic code has been expanded to include selenocysteine as the 21st encoded amino acid (Hatfield et al., 1992b; Hatfield and Diamond, 1993).