NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity
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DOI：
10.1038/nsmb1330
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发表时间：
2008-01-01
影响因子：
16.8
通讯作者：
Le Hir, Herve
中科院分区：
文献类型：
--
作者：
Chamieh, Hala;Ballut, Lionel;Le Hir, Herve
无义介导的mRNA衰变（NMD）通过募集保守的NMD因子UPF1、UPF2和UPF3来消除含有过早翻译终止密码子的mRNA。在人类中，动态组装途径允许UPF1通过外显子连接复合体（EJC）将UPF2和UPF3募集到mRNA中。在这里，我们证明重组EJC核心足以与三种UPF蛋白在RNA上重建稳定的七聚体复合物。EJC蛋白MAGOH， Y14和eIF4AIII为UPF3b提供了一个复合结合位点，作为UPF2和UPF1的桥梁。在UPF三聚体复合体中，UPF2和UPF3b共同刺激UPF1的atp酶和RNA解旋酶活性。这项工作表明，EJC核心足以稳定地将UPF蛋白锚定在mRNA上，并为其中心效应物UPF1的调控提供了见解。
Nonsense-mediated mRNA decay (NMD) eliminates mRNAs containing a premature translation termination codon through the recruitment of the conserved NMD factors UPF1, UPF2 and UPF3. In humans, a dynamic assembly pathway allows UPF1 to join UPF2 and UPF3 recruited to the mRNA by the exon-junction complex (EJC). Here we show that the recombinant EJC core is sufficient to reconstitute, with the three UPF proteins, a stable heptameric complex on RNA. The EJC proteins MAGOH, Y14 and eIF4AIII provide a composite binding site for UPF3b that serves as a bridge to UPF2 and UPF1. In the UPF trimeric complex, UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. This work demonstrates that the EJC core is sufficient to stably anchor the UPF proteins to mRNA and provides insights into the regulation of its central effector, UPF1.