Affiliations: Faculty of Pharmaceutical Sciences, Nagoya City
University, Mizuho-ku, Nagoya 467-8603, Japan
Note: [] PhD, Faculty of Pharmaceutical Sciences, Nagoya City University,
Mizuho-ku, Nagoya 467-8603, Japan. Tel.: +81 52 836 3490; Fax: +81 52 834 9309;
E-mail: [email protected]
Abstract: For eukaryotic selenoprotein mRNAs, it has been proposed that the
SECIS element in the 3'-UTR 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 being considered. Therefore, we searched for a protein which
binds to an RNA sequence surrounding the UGA Sec codon on human GPx mRNA. We
found a protein, prepared from bovine brain microsomes, which strongly bound to
the RNA fragment upstream of the UGA Sec codon but not 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. We also obtained the similar results
with the RNA fragments of type I iodothyronine 5'-deiodinase (5'DI) mRNAs.
Comparison of such RNA fragments with SECIS fragments revealed similarities in
the region upstream of the in-frame UGA Sec codon of several Se-protein mRNAs.
The study thus favoures a novel model of Sec incorporation at the UGA Sec codon
that involves 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.
Keywords: selenocysteine, UGA codon, Selenium, SECIS RNA, elongation factor, SECIS-binding protein
Journal: BioFactors, vol. 14, no. 1-4, pp. 25-35, 2001
