ARE-mRNA degradation requires the 5′-3′ decay pathway
ARE-mRNA degradation requires the 5′-3′ decay pathway
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DOI：
10.1038/sj.embor.7400572
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发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Anderson, P
中科院分区：
文献类型：
--
作者：
Stoecklin, G;Mayo, T;Anderson, P
作为抑制基因表达的一种重要方式，在3'非翻译区含有富含AU的元件（ARE）的信使RNA在细胞质中被迅速降解。ARE介导的mRNA衰变（AMD）由去腺苷化引发，并且体外研究已经表明，随后的降解通过称为外泌体的核酸外切酶复合物以3 '-5'方向发生。mRNA降解的另一途径发生在加工体，即含有去帽酶、5 '-3'核酸外切酶Xrn 1和Lsm 1 -7七聚体的细胞质病灶。为了确定这两种途径中的哪一种对活细胞中的AMD是重要的，我们在人HT 1080细胞中使用短干扰RNA靶向两种途径的组分。我们发现Xrn 1和Lsm 1对AMD是必不可少的。另一方面，在测试的三种外泌体组分中，仅敲低PmScl-75引起AMD的强烈抑制。我们的研究结果表明，哺乳动物细胞，类似于酵母，需要5 '-3 'Xrn1途径降解ARE-mRNA。
As an important mode of suppressing gene expression, messenger RNAs containing an AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in the cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and in vitro studies have indicated that subsequent degradation occurs in the 3'-5' direction through a complex of exonucleases termed the exosome. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. To determine which of the two pathways is important for AMD in live cells, we targeted components of both pathways using short interfering RNA in human HT1080 cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out of three exosome components tested, only knockdown of PmScl-75 caused a strong inhibition of AMD. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.