UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps.
UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps.
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DOI：
10.1016/j.molcel.2010.07.004
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发表时间：
2010-08-13
期刊：
影响因子：
16
通讯作者：
Maquat LE
中科院分区：
文献类型：
--
作者：
Hwang J;Sato H;Tang Y;Matsuda D;Maquat LE
无义介导的mRNA衰变（NMD）是一种mRNA监视机制，在哺乳动物中通常在翻译的先锋轮期间识别提前终止密码子（PTC）时发生。这一轮涉及新合成的mRNA，其在其5'端被帽结合蛋白（CBP）异二聚体CBP 80-CBP 20结合。在这里，我们表明，排除NMD因子UPF 1与CBP 80的结合在两个步骤中抑制NMD：在PTC的SURF复合物形成过程中SMG 1和UPF 1与两个真核释放因子（eRF）的关联，以及SMG 1和UPF 1与外显子连接复合物的后续关联。我们还证明，UPF 1结合PTC的mRNA比相应的PTC-免费的mRNA的方式，促进了UPF 1-CBP 80的相互作用更有效。一个统一的模型提出了一个编排的一系列蛋白质-蛋白质相互作用发生在一个NMD目标。
Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that in mammals generally occurs upon recognition of a premature termination codon (PTC) during a pioneer round of translation. This round involves newly synthesized mRNA that is bound at its 5’ end by the cap-binding protein (CBP) heterodimer CBP80-CBP20. Here, we show that precluding the binding of the NMD factor UPF1 to CBP80 inhibits NMD at two steps: the association of SMG1 and UPF1 with the two eukaryotic release factors (eRFs) during SURF complex formation at a PTC, and the subsequent association of SMG1 and UPF1 with an exon-junction complex. We also demonstrate that UPF1 binds PTC-containing mRNA more efficiently than the corresponding PTC-free mRNA in a way that is promoted by the UPF1-CBP80 interaction. A unifying model proposes a choreographed series of protein-protein interactions occurring on an NMD target.
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