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Selenoproteins are proteins containing the rare amino acid selenocysteine incorporated at specific positions specified by UGA codons in their mRNAs. This chapter summarizes what we know about the functions of the best-studied selenoproteins and presents key phenotypes of mice deficient in specific selenoproteins. We then review the intricate molecular biology of selenocysteine incorporation, which relies on the recoding of the UGA codon as selenocysteine. cis- and trans-Acting factors are involved in selenoprotein biosynthesis. Many open questions remain regarding the exact mechanism of selenoprotein translation and the establishment of a hierarchy among selenoproteins that becomes apparent when dietary selenium supply becomes limited.

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