Chang Yao-Fu, Imam J Saadi, Wilkinson Miles F
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Annu Rev Biochem. 2007;76:51-74. doi: 10.1146/annurev.biochem.76.050106.093909.
Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.
无义介导的mRNA降解（NMD）是一种质量控制机制，可选择性地降解带有提前终止（无义）密码子的mRNA。如果这些mRNA被翻译，它们会产生具有显性负性或有害功能获得活性的截短蛋白。在本综述中，我们描述了NMD的分子机制。我们首先介绍了所有真核生物中已知参与NMD的保守因子。然后，我们描述了一种独特的蛋白质复合物，它在剪接过程中沉积在哺乳动物mRNA上，将终止密码子定义为提前出现的。这种外显子连接复合物（EJC）与在上游终止密码子处组装的NMD因子之间的相互作用触发了一系列最终导致mRNA降解的步骤。我们讨论了这些校对事件是否优先发生在高等和低等真核生物的“先驱”轮翻译过程中、它们在细胞中的位置，以及它们是否可以使用替代的EJC因子或独立于EJC发挥作用。
