RNA Structures Involved in Selenoprotein Synthesis

Abstract

The occurrence of selenocysteine in a protein was first demonstrated for protein A of glycine reductase from Clostridium sticklandii in 1976 (Cone et al. 1976). Cotranslational incorporation of selenocysteine requires the usage of a specific codon, as well as the presence of a special tRNA that can be charged with selenocysteine. The first evidence for the cotranslational incorporation pathway came in 1986, when two selenocysteine-containing enzymes—the formate dehydrogenase H from Escherichia coli (Zinoni et al. 1986) and the glutathione peroxidase from mouse (Chambers et al. 1986)—were found to be encoded by genes with a TGA codon interrupting the open reading frame. Since then, a number of proteins, mostly oxidoreductases, have been identified that contain selenocysteine in the active site. It is now known that selenocysteine incorporation into proteins is always directed by a UGA codon, a feature common to bacteria, archaea, and eukarya.

Genetic analysis of E. coli mutants in which selenocysteine incorporation into proteins is blocked led to the discovery of a novel tRNA with an anticodon complementary to UGA: tRNA^Sec (Leinfelder et al. 1988a). A number of specific tRNAs that are able to decode UGA codons have been identified in bacteria (Heider et al. 1989; Tormay et al. 1994), in protists (Hatfield et al. 1991), in fungi and plants (Hatfield et al. 1992), and throughout the animal kingdom (Lee et al. 1989Lee et al. 1990). In bacteria, these tRNAs are charged with serine, which is then converted to selenocysteine by specific enzymes (Leinfelder et al. 1990; Forchhammer et...