Nonsense-mediated mRNA decay (NMD) mechanisms
Nonsense-mediated mRNA decay (NMD) mechanisms
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DOI：
10.1038/nsmb.1550
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发表时间：
2009-02-01
影响因子：
16.8
通讯作者：
Wen, Jikai
中科院分区：
文献类型：
--
作者：
Brogna, Saverio;Wen, Jikai
无义介导的mRNA衰变（NMD）是一种消除含有过早终止密码子（PTC）的mRNA的终止偶联机制。在哺乳动物细胞中，NMD也与前mRNA剪接有关，因为在许多情况下，只有当PTC位于内含子上游时，才会发生强烈的mRNA减少。有人提出，在这些系统中，外显子连接复合物（EJC）介导剪接和NMD之间的联系。最近的研究质疑剪接和EJC在启动NMD中的作用。相反，他们提出了一个普遍的和进化上保守的机制，其中NMD的主要调节因子是PTC和mRNA的poly（A）尾之间的距离。在这里，我们讨论了新的NMD模型和EJC概念的局限性，我们认为，既不能令人满意地占所有可用的数据，并提供了一个新的模型来测试在未来的研究。
Nonsense-mediated mRNA decay (NMD) is a translation-coupled mechanism that eliminates mRNAs containing premature translation-termination codons (PTCs). In mammalian cells, NMD is also linked to pre-mRNA splicing, as in many instances strong mRNA reduction occurs only when the PTC is located upstream of an intron. It is proposed that in these systems, the exon junction complex (EJC) mediates the link between splicing and NMD. Recent studies have questioned the role of splicing and the EJC in initiating NMD. Instead, they put forward a general and evolutionarily conserved mechanism in which the main regulator of NMD is the distance between a PTC and the poly(A) tail of an mRNA. Here we discuss the limitations of the new NMD model and the EJC concept; we argue that neither satisfactorily accounts for all of the available data and offer a new model to test in future studies.