In mammals, most of the selenium contained in the body is present as an unusual 
amino acid, selenocysteine (Sec), whose codon is UGA. Because the UGA codon is 
typically recognized as a translation stop signal, it is intriguing how a cell 
recognizes and distinguishes a UGA Sec codon from a UGA stop codon. For 
eukaryotic selenoprotein mRNAs, it has been proposed that a conserved stem-loop 
structure designated the Sec insertion sequence (SECIS) in the 3'-untranslated 
(3'-UTR) region is required for recognition of UGA as a Sec codon. Some proteins 
which bind to SECIS (SBP) have been reported. However, it is not clear how the 
SECIS element in the 3'-UTR can mediate Sec insertion far at the in-frame UGA 
Sec codons. The idea that there must be a signal near the UGA Sec codon is still 
considered. Therefore, we searched for a protein which binds to an RNA sequence 
surrounding the UGA Sec codon on human glutathione peroxidase (GPx) mRNA. We 
found a protein which strongly bound to the RNA fragment upstream of the UGA Sec 
codon. However, this protein did not bind to the RNA sequence downstream of the 
UGA codon. This protein also bound to the SECIS sequence in the 3'-UTR of human 
GPx, and this binding to SECIS was competed with the RNA fragment upstream of 
the UGA Sec codon. Comparison of the RNA fragment with the SECIS fragment 
identified the conserved regions, which appeared in the region upstream of the 
in-frame UGA Sec codon of Se-protein mRNAs. Thus, this study proposes a novel 
model to understand the mechanisms of Sec incorporation at the UGA Sec codon, 
especially the regions upstream of the UGA codon of mRNAs of mammalian 
selenoproteins. This model explains that the stem-loop structure covering the 
UGA codon is recognized by SBP and how the UGA Sec codon escapes from attack by 
eRF of the peptide releasing factor.