Brogna Saverio, Wen Jikai
University of Birmingham, School of Biosciences, Edgbaston, Birmingham B15 2TT, UK.
Nat Struct Mol Biol. 2009 Feb;16(2):107-13. doi: 10.1038/nsmb.1550.
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.
无义介导的mRNA降解（NMD）是一种与翻译偶联的机制，可消除含有提前翻译终止密码子（PTC）的mRNA。在哺乳动物细胞中，NMD还与前体mRNA剪接相关，因为在许多情况下，只有当PTC位于内含子上游时，mRNA才会强烈减少。有人提出，在这些系统中，外显子连接复合体（EJC）介导剪接与NMD之间的联系。最近的研究对剪接和EJC在启动NMD中的作用提出了质疑。相反，他们提出了一种普遍且进化保守的机制，其中NMD的主要调节因子是PTC与mRNA的聚腺苷酸尾之间的距离。在这里，我们讨论了新的NMD模型和EJC概念的局限性；我们认为两者都不能令人满意地解释所有现有数据，并提供了一个新模型供未来研究进行测试。
