Threading the needle: Getting selenocysteine into proteins

The co-translational incorporation of selenocysteine (Sec) requires that UGA be recognized as a sense rather than a nonsense codon. This is accomplished by the concerted action of a Sec insertion sequence (SECIS) element, SECIS binding protein 2, and a ternary complex of the Sec specific elongation factor, Sec-tRNA^Sec, and GTP. The mechanism by which they alter the canonical protein synthesis reaction has been elusive. Here we present an overview of the mechanistic perspective on Sec incorporation, highlighting recent advances in the field.