Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA
Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA
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DOI：
10.1038/nsmb1297
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发表时间：
2007-10-01
影响因子：
16.8
通讯作者：
Maquat, Lynne E.
中科院分区：
文献类型：
--
作者：
Matsuda, Daiki;Hosoda, Nao;Maquat, Lynne E.
废话介导的mRNA衰变（NMD）通常会消除过早终止翻译并发生在所有研究的真核生物中的信使RNA，尽管机械变化。在哺乳动物中，NMD似乎仅限于新合成的mRNA，该mRNA受帽结合异二聚体CBP80-CBP20（CBP80/20）的约束，通常至少具有一个外显子连接综合体（EJC） - 拼图。但是，哺乳动物NMD还可以靶向缺乏无义密码子下游的EJC的剪接mRNA。在这里，我们提供的证据表明，这种额外的途径（称为FailSafe NMD）同样仅限于CBP80/20结合的mRNA，并且无法检测到其随后重塑的产品EIF4E结合的mRNA。我们的研究，包括对因子依赖性的分析，揭示了两种哺乳动物 - 细胞NMD途径的重要共享特征，以及哺乳动物和酿酒酵母中NMD之间的基本差异。
Nonsense-mediated mRNA decay (NMD) generally eliminates messenger RNAs that prematurely terminate translation and occurs in all eukaryotes that have been studied, although with mechanistic variations. In mammals, NMD seems to be restricted to newly synthesized mRNA that is bound by the cap-binding heterodimer CBP80-CBP20 (CBP80/20) and typically has at least one exon junction complex (EJC) situated downstream of the nonsense codon and added post-splicing. However, mammalian NMD can also target spliced mRNA lacking an EJC downstream of the nonsense codon. Here we provide evidence that this additional pathway, known as failsafe NMD, likewise seems to be restricted to CBP80/20- bound mRNA and does not detectably target its subsequently remodeled product, eIF4E-bound mRNA. Our studies, including analyses of factor dependence, reveal important shared features of the two mammalian-cell NMD pathways as well as fundamental differences between NMD in mammals and Saccharomyces cerevisiae.