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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes
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The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes

机译：锥虫体内硒代半胱氨酸插入的经典途径是必不可少的

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摘要

The micronutrient selenium is found in proteins as selenocysteine (Sec), the 21st amino acid cotranslationally inserted in response to a UGA codon. In vitro studies in archaea and mouse showed that Sec-tRNA~(Sec) formation is a 3-step process starting with serylation of tRNA~(Sec) by seryl-tRNA synthetase (SerRS), phosphorylation of serine to form phosphoserine (Sep)-tRNA~(Sec) by phosphoseryl-tRNA~(Sec) kinase (PSTK), and conversion to Sec-tRNA~(Sec) by Sep-tRNA:Sec-tRNA synthase (SepSecS). However, a complete study of eukaryotic selenoprotein synthesis has been lacking. Here, we present an analysis of Sec-tRNA~(Sec) formation in the parasitic protozoon Trypanosoma brucei in vivo. Null mutants of either PSTK or SepSecS abolished selenoprotein synthesis, demonstrating the essentiality of both enzymes for Sec-tRNA~(Sec) formation. Growth of the 2 knockout strains was not impaired; thus, unlike mammals, trypanosomes do not require selenoproteins for viability. Analysis of conditional RNAi strains showed that SerRS, selenophosphate synthase, and the Sec-specific elongation factor, EFSec, are also essential for selenoprotein synthesis. These results with T. brucei imply that eukaryotes have a single pathway of Sec-tRNA~(Sec) synthesis that requires Sep-tRNA~(Sec) as an intermediate.
机译：蛋白质中的微量营养元素硒是硒代半胱氨酸（Sec），是响应UGA密码子共翻译插入的第21个氨基酸。在古细菌和小鼠中的体外研究表明，Sec-tRNA〜（Sec）的形成是一个三步过程，开始于通过丝氨酰-tRNA合成酶（SerRS）对tRNA〜（Sec）进行Serlation，将丝氨酸磷酸化以形成磷酸丝氨酸（Sep）。 -tRNA-（Sec）通过磷酸丝氨酰-tRNA-（Sec）激酶（PSTK）合成，并通过Sep-tRNA：Sec-tRNA合酶（SepSecS）转化为Sec-tRNA-（Sec）。但是，缺乏对真核硒蛋白合成的完整研究。在这里，我们目前在体内寄生虫原生动物Trypanosoma brucei中的Sec-tRNA〜（Sec）形成的分析。 PSTK或SepSecS的无效突变体消除了硒蛋白的合成，证明了这两种酶对于Sec-tRNA〜（Sec）形成的必要性。 2种敲除菌株的生长没有受到损害；因此，与哺乳动物不同，锥虫不需要生存所需的硒蛋白。对条件RNAi菌株的分析表明，SerRS，硒磷酸合酶和Sec特异性延伸因子EFSec对硒蛋白的合成也是必不可少的。 T. brucei的这些结果表明，真核生物具有Sec-tRNA〜（Sec）合成的单一途径，需要Sep-tRNA〜（Sec）作为中间体。

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    Eric Aeby; Sotiria Palioura; Mascha Pusnik; Janine Marazzi; Allyson Lieberman; Elisabetta Ullu; Dieter Soell; Andre Schneider;

  • 作者单位

    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland;

    Departments of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114;

    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland;

    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland;

    Departments of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114;

    Departments of Internal Medicine and Cell Biology, Yale University School of Medicine, New Haven, CT 06536-0812;

    Departments of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114 Departments of Chemistry, Yale University, New Haven, CT 06520-8114;

    Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    phosphoseryl-tRNA~(Sec) kinase; selenocysteine tRNA; Sep-tRNA:Sec-tRNA synthase; trypanosoma brucei; selenoprotein;

    机译：磷酸丝氨酰tRNA〜（Sec）激酶;硒代半胱氨酸tRNA;Sep-tRNA：Sec-tRNA合酶;布鲁氏锥虫硒蛋白;

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