| The essential micronutrient selenium is biologically active through the functions of selenoproteins, into which selenium is cotranslationally incorporated as the amino acid selenocysteine in response to some in-frame UGA codons. The interpretation of UGA as selenocysteine rather than as a translation termination signal is inefficient and is dependent on specialized factors including an mRNA stem-loop, called the SECIS element, tRNA[Ser]Sec, and protein factors which bind to the SECIS element.; Because the translation of UGA as selenocysteine increases with increased selenium availability, it was examined as a locus of regulation for selenoprotein levels. The regulation of UGA translation was examined using a specialized reporter construct and cell lines engineered to reflect biological effects of selenium supplementation, independent of selenium levels. The activities of selected selenoproteins, the efficiency of UGA translation, levels of tRNA [Ser]Sec and the distribution of the two tRNA[Ser]Sec isoforms were evaluated to identify conditions that contribute to the selenium induction of selenoprotein translation.; Substantial evidence was presented which indicates that one isoform of tRNA[Ser]Sec is preferentially active in the translation of UGA. It was found that factors other than the SECIS element are likely to be responsible for the differences in selenium sensitivity among selenoproteins. Furthermore, tRNA[Ser]Sec, which can be limiting for selenoprotein translation in some cellular conditions, increases in abundance in response to increased levels of selenoprotein mRNA. These results constitute new information regarding the regulation of selenoprotein translation, and suggest that it involves a complex dynamic among several factors. |
