Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes

Authors

Xue-Ming Xu, National Institutes of Health, Bethesda, MDFollow
Bradley A. Carlson, National Institutes of Health, Bethesda, MDFollow
Heiko Mix, University of Nebraska-Lincoln
Yan Zhang, University of Nebraska-LincolnFollow
Kazima Saira, University of Nebraska-Lincoln
Richard S. Glass, University of Arizona, Tucson, Arizona, United States of America
Marla J. Berry, University of Hawaii at Manoa, Honolulu, Hawaii, United States
Vadim Gladyshev, University of Nebraska-LincolnFollow
Dolph L. Hatfield, National Institutes of Health, Bethesda, MDFollow

Date of this Version

January 2007

Comments

Published in PLoS Biology | January 2007 | Volume 5 | Issue 1. Permission to use. www.plosbiology.org

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 Ophosphoseryl- 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, Ophosphoseryl- 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.