Recognition of UGA as a selenocysteine codon in Type I deiodinase requires sequences in the 3′ untranslated region
- 19 September 1991
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 353 (6341), 273-276
- https://doi.org/10.1038/353273a0
Abstract
SELENOCYSTEINE is incorporated cotranslationally at UGA codons, normally read as stop codons, in several bacterial proteins1,2 and in the mammalian proteins glutathione peroxidase (GPX)3–5, selenoprotein P6 and Type Iiodothyronine 5′ deiodinase (5′DI)7. Previous analyses in bacteria have suggested that a stem–loop structure involving the UGA codon and adjacent sequences is necessary and sufficient for selenocysteine incorporation into formate dehydrogenase and glycine reductase2,8,9. We used the recently cloned 5′DI to investigate selenoprotein synthesis in eukaryotes. We show that successful incorporation of seleno-cysteine into this enzyme requires a specific 3′ untranslated (3′ut) segment of about 200 nucleotides, which is found in both rat and human 5′DI messenger RNAs. These sequences are not required for expression of a cysteine-mutant deiodinase. Although there is little primary sequence similarity between the 3′ut regions of these mRNAs and those encoding GPX, the 3′ut sequences of rat GPX can substitute for the 5′DI sequences in directing selenocysteine insertion. Computer analyses predict similar stem-loop structures in the 3′ut regions of the 5′DI and GPX mRNAs. Limited mutations in these structures reduce or eliminate their capacity to permit 5′DI translation. These results identify a 'selenocysteine-insertion sequence' motif in the 3′ut region of these mRNAs that is essential for successful translation of 5′DI, presumably GPX, and possibly other eukaryotic selenocysteine-containing proteins.Keywords
This publication has 15 references indexed in Scilit:
- Selenoprotein A component of the glycine reductase complex from Clostridium purinolyticum: nucleotide sequence of the gene shows that selenocysteine is encoded by UGAJournal of Bacteriology, 1991
- Selenocysteine: the 21st amino acidMolecular Microbiology, 1991
- Type I iodothyronine deiodinase is a selenocysteine-containing enzymeNature, 1991
- Primary Structure of Human Plasma Glutathione Peroxidase Deduced from eDNA Sequences1The Journal of Biochemistry, 1990
- Features of the formate dehydrogenase mRNA necessary for decoding of the UGA codon as selenocysteine.Proceedings of the National Academy of Sciences of the United States of America, 1990
- Mutations of the Rat Growth Hormone Promoter which Increase and Decrease Response to Thyroid Hormone Define a Consensus Thyroid Hormone Response ElementMolecular Endocrinology, 1989
- Selenocysteine's mechanism of incorporation and evolution revealed in cDNAs of three glutathione peroxidasesProtein Engineering, Design and Selection, 1988
- Nucleotide sequence of a rat glutathione peroxidase cDNANucleic Acids Research, 1988
- Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system.Proceedings of the National Academy of Sciences of the United States of America, 1987
- Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogen-lyase-linked) from Escherichia coli.Proceedings of the National Academy of Sciences, 1986