Biosynthesis of selenocysteine on its tRNA in eukaryotes

Xue Ming Xu; Bradley A. Carlson; Heiko Mix; Yan Zhang; Kazima Saira; Richard S. Glass; Marla J. Berry; Vadim N. Gladyshev; Dolph L. Hatfield

doi:10.1371/journal.pbio.0050004

Biosynthesis of selenocysteine on its tRNA in eukaryotes

Xue Ming Xu, Bradley A. Carlson, Heiko Mix, Yan Zhang, Kazima Saira, Richard S. Glass, Marla J. Berry, Vadim N. Gladyshev, Dolph L. Hatfield

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

236 Scopus citations

Abstract

Selenocysteine (Sec) is cotranslationally inserted into protein in response to UGA codons and is the 21st amino acid in the genetic code. However, the means by which Sec is synthesized in eukaryotes is not known. Herein, comparative genomics and experimental analyses revealed that the mammalian Sec synthase (SecS) is the previously identified pyridoxal phosphate-containing protein known as the soluble liver antigen. SecS required selenophosphate and O-phosphoseryl-tRNA^[Ser]Sec as substrates to generate selenocysteyl-tRNA^[Ser]Sec. Moreover, it was found that Sec was synthesized on the tRNA scaffold from selenide, ATP, and serine using tRNA ^[Ser]Sec, seryl-tRNA synthetase, O-phosphoseryl-tRNA ^[Ser]Sec kinase, selenophosphate synthetase, and SecS. By identifying the pathway of Sec biosynthesis in mammals, this study not only functionally characterized SecS but also assigned the function of the O-phosphoseryl- tRNA^[Ser]Sec kinase. In addition, we found that selenophosphate synthetase 2 could synthesize monoselenophosphate in vitro but selenophosphate synthetase 1 could not. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that synthesize selenoproteins.

Original language	English (US)
Pages (from-to)	96-105
Number of pages	10
Journal	PLoS biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1371/journal.pbio.0050004
State	Published - Jan 2007

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Agricultural and Biological Sciences

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title = "Biosynthesis of selenocysteine on its tRNA in eukaryotes",

abstract = "Selenocysteine (Sec) is cotranslationally inserted into protein in response to UGA codons and is the 21st amino acid in the genetic code. However, the means by which Sec is synthesized in eukaryotes is not known. Herein, comparative genomics and experimental analyses revealed that the mammalian Sec synthase (SecS) is the previously identified pyridoxal phosphate-containing protein known as the soluble liver antigen. SecS required selenophosphate and O-phosphoseryl-tRNA[Ser]Sec as substrates to generate selenocysteyl-tRNA[Ser]Sec. Moreover, it was found that Sec was synthesized on the tRNA scaffold from selenide, ATP, and serine using tRNA [Ser]Sec, seryl-tRNA synthetase, O-phosphoseryl-tRNA [Ser]Sec kinase, selenophosphate synthetase, and SecS. By identifying the pathway of Sec biosynthesis in mammals, this study not only functionally characterized SecS but also assigned the function of the O-phosphoseryl- tRNA[Ser]Sec kinase. In addition, we found that selenophosphate synthetase 2 could synthesize monoselenophosphate in vitro but selenophosphate synthetase 1 could not. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that synthesize selenoproteins.",

author = "Xu, {Xue Ming} and Carlson, {Bradley A.} and Heiko Mix and Yan Zhang and Kazima Saira and Glass, {Richard S.} and Berry, {Marla J.} and Gladyshev, {Vadim N.} and Hatfield, {Dolph L.}",

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AU - Xu, Xue Ming

AU - Carlson, Bradley A.

AU - Mix, Heiko

AU - Zhang, Yan

AU - Saira, Kazima

AU - Glass, Richard S.

AU - Berry, Marla J.

AU - Gladyshev, Vadim N.

AU - Hatfield, Dolph L.

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Biosynthesis of selenocysteine on its tRNA in eukaryotes

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