Decoding UGA as selenocysteine requires a unique tRNA, a specialized elonga
tion factor, and specific secondary structures in the mRNA, termed SECIS el
ements. Eukaryotic SECIS elements are found in the 3' untranslated region o
f selenoprotein mRNAs while those in prokaryotes occur immediately downstre
am of UGA. Consequently, a single eukaryotic SECIS element can serve multip
le UGA codons, whereas prokaryotic SECIS elements only function for the adj
acent UGA, suggesting distinct mechanisms for recoding in the two kingdoms.
We have identified and characterized the first eukaryotic selenocysteyl-tR
NA-specific elongation factor. This factor forms a complex with mammalian S
ECIS binding protein 2, and these two components function together in selen
ocysteine incorporation in mammalian cells. Expression of the two functiona
l domains of the bacterial elongation factor-SECIS binding protein as two s
eparate proteins in eukaryotes suggests a mechanism for rapid exchange of c
harged for uncharged selenocysteyl-tRNA-elongation factor complex, allowing
a single SECIS element to serve multiple UGA codons.