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A model for Sec incorporation with the regions upstream of the UGA Sec codon to play a key role
Author(s) -
Goto Chiharu,
Osaka Takashi,
Mizutani Takaharu
Publication year - 2001
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520140105
Subject(s) - start codon , stop codon , messenger rna , untranslated region , genetics , biology , rna , open reading frame , peptide sequence , gene
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.