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An RNA element that stabilizes translation termination in Rous sarcoma virus.

机译:稳定劳斯肉瘤病毒翻译终止的RNA元件。

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摘要

The nonsense-mediated mRNA decay pathway is a cellular quality control pathway that eliminates mRNAs bearing a premature translation termination codon. Unspliced Rous sarcoma virus RNAs are subject to NMD when a premature termination codon interrupts the viral gag gene. Translation termination at the end of the gag gene does not cause this turnover due to proximity to a downstream stabilizing element that we have termed the RSV stability element (RSE). Deletion of the RSE destabilized the unspliced viral RNA. This destabilization was alleviated by arresting translation or coexpressing a dominant negative form of the protein Upf1, implicating aspects of the nonsense mediated mRNA decay pathway. Additionally, a functional fragment of the RSE can be moved after a PTC in the gag gene to prevent NMD. Interestingly, the RSE cannot stabilize termination in a spliced beta-globin RNA. A two-dimensional model describing the secondary structure of this RNA was predicted based on experimental data. The RSE is structured, and possesses several regions necessary for function. None of the other RSV genes are associated with a downstream stability element that functions like the RSE. Interestingly, a region after the gag gene of HIV-1 was able to stabilize RSV RNAs with termination codons in the gag gene, although HIV itself appears immune to NMD.
机译:无义介导的mRNA衰变途径是一种细胞质量控制途径,可消除带有过早翻译终止密码子的mRNA。当过早的终止密码子中断病毒gag基因时,未剪接的劳斯肉瘤病毒RNA会受到NMD的攻击。由于邻近下游稳定元件(我们称为RSV稳定元件(RSE)),gag基因末端的翻译终止不会导致这种转换。 RSE的删除使未剪接的病毒RNA不稳定。通过停止翻译或共表达蛋白Upf1的显性负向形式来缓解这种不稳定现象,这牵涉到无意义的介导的mRNA衰变途径的各个方面。另外,可以在gag基因中的PTC之后移动RSE的功能片段,以防止NMD。有趣的是,RSE无法稳定剪接的β-珠蛋白RNA中的终止。根据实验数据预测了描述该RNA二级结构的二维模型。 RSE是结构化的,并具有功能所需的多个区域。其他RSV基因均未与功能类似于RSE的下游稳定元件相关。有趣的是,尽管HIV本身似乎对NMD免疫,但在HIV-1的gag基因之后的区域能够通过gag基因中的终止密码子稳定RSV RNA。

著录项

  • 作者

    Weil, Jason E.;

  • 作者单位

    The Johns Hopkins University.;

  • 授予单位 The Johns Hopkins University.;
  • 学科 Biology Molecular.; Biology Virology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 151 p.
  • 总页数 151
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;
  • 关键词

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