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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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编程的翻译阅读产生抗血管原体VEGF-Ax.

Sandeepa M Eswarappa1, Alka A Potdar2, William J Koch1

  • 1Department of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

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概括

哺乳动物细胞利用编程翻译读通 (PTR) 来从血管内皮生长因子A (VEGFA) mRNA中产生新的VEGF-Ax蛋白异型. 这种新发现的机制揭示了一个独特的抗血管生成因子,它对人类组织和疾病有重大影响.

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科学领域:

  • 分子生物学分子生物学
  • 遗传学 是一个遗传学.
  • 生物化学 生物化学

背景情况:

  • 翻译读透扩展了简单的生物体的蛋白质体,通过延伸翻译过去的停止编码.
  • 血管内皮生长因子A (VEGF-A) 是血管生成的关键调节者.

研究的目的:

  • 在哺乳动物细胞中研究编程转化读透 (PTR).
  • 为了识别由PTR产生的新型蛋白质异型及其功能.

主要方法:

  • 对VEGFA mRNA 3' UTR cis作用元素的分析.
  • 使用 hnRNP A2/B1.1 来识别参与 PTR 的 RNA 结合蛋白.
  • 对VEGF-Ax抗血管性活性进行功能性测试.
  • 对额外的读透目标进行全基因组分析.

主要成果:

  • 在哺乳动物内皮细胞中发现了编程翻译读通 (PTR),从VEGFA mRNA生成VEGF-Ax.
  • 在 VEGFA 3' UTR 和 hnRNP A2/B1 中确定了一种 cis 作用元素,该元素对于指导 UGA 停止编码子的血清解码至关重要.
  • VEGF-Ax表现出抗血管新生性质,与VEGF-A的血管新生作用形成鲜明对比.
  • 在人体组织中表达VEGF-Ax,但在结肠腺癌中枯竭;AGO1和MTCH2被确定为其他读透标.

结论:

  • 在脊椎动物中揭示了一种新的蛋白调节的PTR机制.
  • VEGF-Ax代表了一种新的抗血管生成因子,在人类健康和疾病中具有潜在的作用.
  • 在哺乳动物系统中确定了转化读透的新目标和调节者.