Mammalian and other eukaryotic selenocysteine tRNAs

Abstract

Selenocysteine (Sec) tRNA occupies a prominent position in the expression of selenoproteins as it is essential for their synthesis and it provides the means by which selenium is co-translationally inserted into protein as the amino acid, Sec. Thus, Sec tRNA is regarded as the principle constituent in selenoprotein synthesis. Many features unique to this tRNA have been characterized over the years in mammals and other eukaryotes. In the last five years, the major advances have been in an elucidation of the different roles that the two major Sec tRNA isoforms play in selenoprotein biosynthesis and in Sec biosynthesis. One isoform appears to be responsible for the synthesis of selenoproteins that have roles in housekeeping functions and are less dependent on selenium status for their expression. The second isoform, that differs by only a single methyl group at the 2′-O-hydroxyl-ribosyl moiety at position 34 (designated Um34), appears to be responsible for the expression of selenoproteins that have roles in stress-related phenomena and are highly dependent on selenium for their expression. Several new observations regarding Sec biosynthesis, which occurs on its tRNA, have also been recently made. Other recent advances involving Sec tRNA have used this molecule as a tool for determining whether eukaryotes outside the animal kingdom contain the machinery dedicated for the insertion of See into protein. These recent findings are discussed in this chapter. IRI is also affiliated with the Nutritional Science Research Group, Division of Cancer