Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII
Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII
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DOI：
10.1074/jbc.m109.009985
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发表时间：
2009-08-28
影响因子：
4.8
通讯作者：
Liu, Jun O.
中科院分区：
文献类型：
--
作者：
Dang, Yongjun;Low, Woon-Kai;Liu, Jun O.
哺乳动物细胞中无义介导的mRNA衰变（NMD）是去除含有提前终止密码子的mRNA的关键机制，并且由与外显子连接复合物动态相关的许多蛋白质的协调功能介导。然而，这些相互作用所传达的信息以及从机械角度来看的功能后果并没有完全记录下来。在此，我们报告，天然产物帕特胺A（PatA）能够抑制NMD通过直接与eIF4AIII，这是独立的抑制翻译起始的相互作用。此外，我们的特点PatA和放线菌酮调节NMD的机制。与CHX不同，PatA被发现通过一种新的机制抑制NMD，该机制独立于上移码蛋白1的磷酸化。
Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A ( PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulate NMD. Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.