THE ROLE OF SELENIUM IN CELLULAR METABOLISM

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Selenium is essential in the human diet and excesses or deficiencies of this element within a narrow range are detrimental to health. There is substantial evidence supporting a role of selenium in alleviating cancer and heart disease and a role in delaying the aging process. Since this element exerts its effects, at least in part, as a constituent of protein, our goal is to understand how selenium is incorporated into protein. Thus, we are examining the tRNAs that donate selenium in the form of selenocysteine to protein. Interestingly, selenocysteine is biosynthesized on selenocysteine tRNA which is first aminoacylated with serine. In the past year, we have shown that the identity elements in selenocysteine tRNA and serine tRNA for seryl-tRNA synthetase are located principally in the discriminator base at position 73 and in the long extra arm of both tRNAs. The long extra arm acts in an orientation- and length-specific manner in serine tRNA, and in addition, in a sequence- specific manner in selenocysteine tRNA. The other domains of these tRNAs (i.e., the acceptor, D and T stems) contribute to the recognition process, but not to the extent of the discriminator base and the long extra arm. We have also shown unequivocally that the same synthetase and at least some of the same recognition sites are used in aminoacylating both tRNAs. In addition, we have shown that either UUA (a leucine codon) or UAA (a nonsense codon) can serve for inserting selenocysteine into protein provided the selenocysteine tRNA contains an anticodon complementary to the corresponding codon. This observation very importantly demonstrates that UGA, which is the codon for selenocysteine, is not the critical element for selenocysteine insertion into protein. We have also found that the A box and B box, which are the internal control regions for expression of all eukaryotic tRNA genes, are not involved in selenocysteine tRNA gene transcription. However, these internal elements do play a role in processing of the trailer sequence.