Eukaryotes require a selenocysteine (Sec) insertion sequence (SECIS) element in the 3' untranslated region of the mRNA to decode the UGA codon as Sec. SECIS-binding protein 2 (SBP-2) specifically binds selenoprotein mRNAs to form a functional complex and is essential for the insertion of Sec into selenoproteins. Purified SBP-2 interacts specifically with the SECIS element in the phospholipid hydroperoxide glutathione peroxidase mRNA. SBP-2 shows binding activity in the liver and testis as well as hepatoma cells. SBP-2 binds to a conserved RNA binding domain shared with several ribosomal proteins and eukaryotic translation termination release factor 1. A second domain located N-terminal to the RNA binding domain required for Sec insertion allows SBP-2 to stably associate with the ribosomal fraction of cells. SBP-2 preferentially stimulates incorporation directed by the selenoprotein P and phospholipid hydroperoxide glutathione peroxidase SECIS elements. SBP-2 may have a distinct function in selecting the ribosomes for Sec insertion.
