Identification of a novel translation factor necessary for the incorporation of selenocysteine into protein

Abstract

DURING the biosynthesis of selenoproteins in both prokaryotes and eukaryotes, selenocysteine is cotranslationally incorporated into the nascent polypeptide chain^{1, 2} through a process directed by a UGA codon that normally functions as a stop codon^3–5. Recently, four genes have been identified whose products are required for selenocysteine incorporation in Escherichia coli⁶. One of these genes,selC, codes for a novel transfer RNA species (tRNA^UCA) that accepts serine and cotranslationally inserts selenocysteine by recognizing the specific UGA codon⁷. The serine residue attached to this tRNA is converted to selenocysteine in a reaction dependent on functional selA and selD gene products⁸. By contrast, the selB gene product (SELB) is not required until after selenocysteyl-tRNA biosynthesis⁸. Here we present evidence indicating that SELB is a novel translation factor. The deduced amino-acid sequence of SELB exhibits extensive homology with the sequences of the translation initiation factor-2 (IF-2) and elongation factor Tu (EF-Tu). Furthermore, purified SELB protein binds guanine nucleotides in a 1:1 molar ratio and specifically complexes selenocysteyl-tRNA^UCA, but does not interact with seryl-tRNA^UCA. Thus, SELB could be an amino acid-specific elongation factor, replacing EF-Tu in a special translational step.