SELENOPROTEINS, SELENOPROTEIN mRNA EXPRESSION, FERTILITY, AND MORTALITY

Selenocysteine is a rare amino acid in protein that is encoded by UGA with the requirement of a downstream mRNA stem-loop structure, the selenocysteine insertion sequence element. To detect selenoproteins in Drosoph- ila, the entire genome was analyzed with a novel pro- gram that searches for selenocysteine insertion se- quence elements, followed by selenoprotein gene signature analyses. This computational screen and sub- sequent metabolic labeling with 75Se and characteriza- tion of selenoprotein mRNA expression resulted in iden- tification of three selenoproteins: selenophosphate synthetase 2 and novel G-rich and BthD selenoproteins that had no homology to known proteins. To assess a biological role for these proteins, a simple chemically defined medium that supports growth of adult Drosoph- ila and requires selenium supplementation for optimal survival was devised. Flies survived on this medium supplemented with 108 to 106 M selenium or on the commonly used yeast-based complete medium at about twice the rate as those on a medium without selenium or with >106 M selenium. This effect correlated with changes in selenoprotein mRNA expression. The num- ber of eggs laid by Drosophila was reduced approxi- mately in half in the chemically defined medium com- pared with the same medium supplemented with selenium. The data provide evidence that dietary sele- nium deficiency shortens, while supplementation of the diet with selenium normalizes the Drosophila life span by a process that may involve the newly identified selenoproteins.