An RNA-Binding Protein Recognizes a Mammalian Selenocysteine Insertion Sequence Element Required for Cotranslational Incorporation of Selenocysteine

Lesoon, Andrea; Ac, Mehta; Singh, Raju; Chisolm, Guy M.; Driscoll, Donna M.

doi:10.1128/mcb.17.4.1977

Cited by 78 publications

(70 citation statements)

References 34 publications

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“…Using gel shift experiments, various proteins that bind to eukaryotic SECIS structures were detected. The bands, however, differ in molecular masses (from 48 -120 kDa) and their affinities to SECIS elements of a given selenoprotein mRNA could usually not be compared to that of other SECIS elements (Shen et al, 1995(Shen et al, , 1998Yamada, 1995;Hubert et al, 1996;Lesoon et al, 1997). A protein of 120 kDa was reported to be required for eukaryotic selenoprotein biosynthesis (Copeland et al, 2000).…”

Section: The Biosynthesis Of Selenoproteinsmentioning

confidence: 99%

Selenium in Biology: Facts and Medical Perspectives

Köhrl¹,

Brigelius‐Flohé²,

Böck³

et al. 2000

Biological Chemistry

240

143

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Several decades after the discovery of selenium as an essential trace element in vertebrates approximately 20 eukaryotic and more than 15 prokaryotic selenoproteins containing the 21 st proteinogenic amino acid, selenocysteine, have been identified, partially characterized or cloned from several species. Many of these proteins are involved in redox reactions with selenocysteine acting as an essential component of the catalytic cycle. Enzyme activities have been assigned to the glutathione peroxidase family, to the thioredoxin reductases, which were recently identified as selenoproteins, to the iodothyronine deiodinases, which metabolize thyroid hormones, and to the selenophosphate synthetase 2, which is involved in selenoprotein biosynthesis. Prokaryotic selenoproteins catalyze redox reactions and formation of selenoethers in (stress-induced) metabolism and energy production of E. coli, of the clostridial cluster XI and of other prokaryotes. Apart from the specific and complex biosynthesis of selenocysteine, selenium also reversibly binds to proteins, is incorporated into selenomethionine in bacteria, yeast and higher plants, or posttranslationally modifies a catalytically essential cysteine residue of CO dehydrogenase. Expression of individual eukaryotic selenoproteins exhibits high tissue specificity, depends on selenium availability, in some cases is regulated by hormones, and if impaired contributes to several pathological conditions. Disturbance of selenoprotein expression or function is associated with deficiency syndromes (Keshan and Kashin-Beck disease), might contribute to tumorigenesis and atherosclerosis, is altered in several bacterial and viral infections, and leads to infertility in male rodents.

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Section: The Biosynthesis Of Selenoproteinsmentioning

confidence: 99%

Selenium in Biology: Facts and Medical Perspectives

Köhrl¹,

Brigelius‐Flohé²,

Böck³

et al. 2000

Biological Chemistry

240

143

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“…In particular, dbpB differs from the prokaryotic SELB protein (44) in that it does not contain any elongation factor domains; therefore that function probably involves another factor, such as one of the other specific SECIS-binding proteins that have been identified by gel shift and UV-crosslinking studies (15,16). A 60 -65-kDa protein in human and rat cells binds the SECIS elements from both rat glutathione peroxidase and rat type I iodothyronine 5Ј-deiodinase transcripts, with somewhat higher affinity for the former (15).…”

Section: Secis-binding Protein: Bifunctional Role For Dbpb 5445mentioning

confidence: 99%

“…It contains only three very short highly conserved sequences (11,12). We (14) and others (15,16) have identified cytoplasmic binding factors in mammalian cells that specifically recognize the SECIS element.…”

mentioning

confidence: 99%

Identification and Molecular Cloning of a Human Selenocysteine Insertion Sequence-binding Protein

Shen

Leonard

et al. 1998

Journal of Biological Chemistry

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Prokaryotic and eukaryotic cells incorporate the unusual amino acid selenocysteine at a UGA codon, which conventionally serves as a termination signal. Translation of eukaryotic selenoprotein mRNA requires a nucleotide selenocysteine insertion sequence in the 3-untranslated region. We report the molecular cloning of the binding protein that recognizes the selenocysteine insertion sequence element in human cellular glutathione peroxidase gene (GPX1) transcripts and its identification as DNA-binding protein B, a member of the EFI A / dbpB/YB-1 family. The predicted amino acid sequence contains four arginine-rich RNA-binding motifs, and one segment shows strong homology to the human immunodeficiency virus Tat domain. Recombinant DNAbinding protein B binds the selenocysteine insertion sequence elements from the GPX1 and type I iodothyronine 5-deiodinase genes in RNA electrophoretic mobility shift assays and competes with endogenous GPX1 selenocysteine insertion sequence binding activity in COS-1 cytosol extracts. Addition of antibody to DNAbinding protein B to COS-1 electromobility shift assays produces a slowly migrating "supershift" band. The molecular cloning and identification of DNA-binding protein B as the first eukaryotic selenocysteine insertion sequence-binding protein opens the way to the elucidation of the entire complex necessary for the alternative reading of the genetic code that permits translation of selenoproteins.Both prokaryotic and eukaryotic cells incorporate the sulfurlike element selenium into polypeptides by the translational insertion of the unique amino acid selenocysteine. Most selenoproteins are enzymes that contain a single selenocysteine moiety within the active site; examples include the bacterial formate dehydrogenases (1, 2), the mammalian glutathione peroxidase family (3-6), and the iodothyronine deiodinase family (7). In both prokaryotic and eukaryotic mRNA transcripts, selenocysteine is encoded by a UGA codon, which conventionally serves as one of the three translation termination signals (8, 9). The mechanism for this alternative reading of the genetic code differs in prokaryotes and eukaryotes. In bacterial cells, translation of the UGA codon in transcripts for selenoenzymes such as Escherichia coli formate dehydrogenase depends upon the SELB gene product, which specifically recognizes a short sequence element that is located immediately 3Ј to the UGA and forms a hairpin secondary structure (10). In contrast, translation of eukaryotic selenoprotein mRNA depends upon an 80 -90-nucleotide sequence element in the 3Ј-untranslated region (11,12). This selenocysteine insertion sequence (SECIS) 1 forms a well conserved secondary structure predicted by RNA folding programs to form a stem loop (11, 12) but probably more complex in its configuration (13). It contains only three very short highly conserved sequences (11, 12). We (14) and others (15, 16) have identified cytoplasmic binding factors in mammalian cells that specifically recognize the SECIS element.We now report the first molec...

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“…These functions include SECIS binding, Sec incorporation and ribosome binding. SBP2 binds specifically to the SECIS core as demonstrated by both mutagenesis of the SECIS element and RNA footprinting (Lesoon et al, 1997;Fletcher et al, 2001). SBP2 binding is not affected by mutations in the conserved AAR motif, leaving this part of the SECIS with no known function or binding partner.…”

Section: Sbp2mentioning

confidence: 99%

Regulation of gene expression by stop codon recoding: selenocysteine

Copeland¹

2003

Gene

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The regulation of gene expression at the translational level not only allows for rapid changes in specific protein levels but also provides an opportunity to alter codon specificity. For the incorporation of selenocysteine (Sec) into protein, the UGA codon is transformed from one that signals translation termination to one specific for Sec. This review provides a look at Sec incorporation from the perspective of the individual steps involved in protein synthesis: initiation, elongation and termination. The roles of the factors known to be required for Sec incorporation are considered in the context of each step in translation including structural modeling of the differences between the standard elongation factor eEF1A and the Sec-specific counterpart, eEFSec.

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An RNA-Binding Protein Recognizes a Mammalian Selenocysteine Insertion Sequence Element Required for Cotranslational Incorporation of Selenocysteine

Cited by 78 publications

References 34 publications

Selenium in Biology: Facts and Medical Perspectives

Selenium in Biology: Facts and Medical Perspectives

Identification and Molecular Cloning of a Human Selenocysteine Insertion Sequence-binding Protein

Regulation of gene expression by stop codon recoding: selenocysteine

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