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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa
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DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa

机译:DCP1形成不对称的三聚体,组装成后生动物中的活性mRNA脱盖复合物

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摘要

DCP1 stimulates the decapping enzyme DCP2, which removes the mRNA 5' cap structure committing mRNAs to degradation. In multicellular eukaryotes, DCP1-DCP2 interaction is stabilized by additional proteins, including EDC4. However, most information on DCP2 activation stems from studies in S. cerevisiae, which lacks EDC4. Furthermore, DCP1 orthologs from multicellular eukaryotes have a C-terminal extension, absent in fungi. Here, we show that in metazoa, a conserved DCP1 C-terminal domain drives DCP1 trim-erization. Crystal structures of the DCP1-trimerization domain reveal an antiparallel assembly comprised of three kinked α-helices. Trimerization is required for DCP1 to be incorporated into active decapping complexes and for efficient mRNA decapping in vivo. Our results reveal an unexpected connectivity and complexity of the mRNA decapping network in multicellular eukaryotes, which likely enhances opportunities for regulating mRNA degradation.
机译:DCP1刺激去盖酶DCP2,该酶去除了使mRNA降解的mRNA 5'帽结构。在多细胞真核生物中,DCP1-DCP2相互作用被包括EDC4在内的其他蛋白质所稳定。但是,有关DCP2激活的大多数信息都来自酿酒酵母中的研究,而缺少EDC4。此外,来自多细胞真核生物的DCP1直向同源物具有C端延伸,在真菌中不存在。在这里,我们显示在后生动物中,保守的DCP1 C端域驱动DCP1修剪。 DCP1三聚结构域的晶体结构揭示了由三个扭结的α螺旋组成的反平行装配。三聚化是将DCP1掺入有效的去壳复合物中和体内有效的mRNA去壳所必需的。我们的结果揭示了多细胞真核生物中意想不到的连接性和mRNA脱壳网络的复杂性,这可能会增加调节mRNA降解的机会。

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  • 作者单位

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany;

  • 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
  • 中图分类
  • 关键词

    DCP2; miRNAs; P-bodies; EDC4; Ge-1;

    机译:DCP2;miRNA;P体;EDC4;1号;

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