Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
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DOI：
10.1101/gad.1389006
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发表时间：
2006-02-01
影响因子：
10.5
通讯作者：
Ohno, S
中科院分区：
文献类型：
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作者：
Kashima, I;Yamashita, A;Ohno, S
无义介导的mRNA衰变（NMD）是一种降解含有过早终止密码子（ptc）的mRNA的监视机制。在哺乳动物细胞中，ptc的识别需要翻译，并且依赖于剪接依赖外显子连接复合体（EIC）在mRNA上的存在。虽然已知触发NMD的一个关键事件是SMG-1对反式作用因子Upf1的磷酸化，但Upf1磷酸化与PTC识别之间的关系仍未确定。在这里，我们发现SMG-1与EIC、Upf2、Upf3b、eIF4A3、Magoh和Y14的mrna相关成分结合。此外，我们描述了一个包含NMD因子SMG-1和Upf1以及翻译终止释放因子eRF1和eRF3 （SURF）的新复合物。重要的是，smg -1介导的Upf1磷酸化和NMD需要SURF和EIC之间的关联。因此，smg -1介导的Upf1磷酸化发生在SURF与EJC的关联上，这提供了EJC与ptc识别之间的联系并触发NMD。
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA containing premature termination codons (PTCs). In mammalian cells, recognition of PTCs requires translation and depends on the presence on the mRNA with the splicing-dependent exon junction complex (EIC). While it is known that a key event in the triggering of NMD is phosphorylation of the trans-acting factor, Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition remains undetermined. Here we show that SMG-1 binds to the mRNA-associated components of the EIC, Upf2, Upf3b, eIF4A3, Magoh, and Y14. Further, we describe a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation termination release factors eRF1 and eRF3 (SURF). Importantly, an association between SURF and the EIC is required for SMG-1-mediated Upf1 phosphorylation and NMD. Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD.