一个死亡化负反机制控制着介质转化阶段的停止
1Centre for Genomic Regulation (CRG), Pompeu Fabra University (UPF), C/Dr Aiguader 88, 08003, Barcelona, Spain.
Nature
|April 4, 2008
概括
卵子细胞中的 meiotic 进展依赖于定时的mRNA 翻译,由多基和死基控制. 这项研究确定了C3H-4,这是一种调节mRNA死亡化的蛋白质,确保了适当的介质阶段过渡.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 在脊椎动物卵细胞中, meiotic 的进展取决于母体mRNAs 的调节翻译.
- 细胞质多化,由细胞质多化元素 (CPE) 介导,对于在卵细胞成熟期间激活mRNA转化至关重要.
- 这个过程对于激活促进成熟的因素和进入介质阶段MI和MII至关重要.
研究的目的:
- 为了识别在介质阶段过渡过程中经历细胞质多基化的新型mRNA.
- 研究新发现的调控元素和蛋白质在调控变过程中的mRNA转化中的作用.
- 阐明控制关键介质调节者的精确mRNA激活时间的机制.
主要方法:
- 卵细胞的全基因组功能查,以识别细胞质多基化mRNAs.
- 对调节元素的mRNA序列的分析,如细胞质多化元素 (CPEs) 和 (A+U) 丰富元素 (ARE).
- 涉及C3H-4蛋白的功能性研究,包括其在化过程中的积累及其消去的影响.
主要成果:
- 确定了大量具有CPE和ARE的mRNA,这表明双重调节.
- 作为ARE结合蛋白的C3H-4的mRNA在介质变异I期间积累,其缺失导致介质停止.
- C3H-4 招募了 CCR4 死亡酶复合体,导致多A 尾部缩短,这种机制与 CPEs 一起微调了阿纳法酶促进复合抑制剂 (Emi1 和 Emi2) 的转化.
结论:
- 细胞质多化早期的波动激活了涉及C3H-4合成的负反循环.
- C3H-4将死乙酶复合物招募到特定的mRNA中,调节多甲尾长度和翻译时间.
- 这种反循环对于输出基因相,相互作用和卵细胞中整体介质进展至关重要.
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