A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding
A mechanism of translational repression by competition of Paip2 with eIF4G for poly(A) binding protein (PABP) binding
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DOI：
10.1073/pnas.0603701103
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发表时间：
2006-06-20
影响因子：
11.1
通讯作者：
Sonenberg, Nahum
中科院分区：
文献类型：
--
作者：
Karim, Muhammad M.;Svitkin, Yuri V.;Sonenberg, Nahum
真核mRNA 3' poly（A）尾和5'帽协同增强翻译。这种相互作用由帽结合蛋白eIF 4 E、多聚腺苷酸结合蛋白（PABP）和eIF 4G介导，eIF 4G是一种桥接ORE和PABP以实现mRNA环化的支架蛋白。翻译抑制子Paip 2（PABP相互作用蛋白2）通过促进PABP从poly（A）解离来抑制翻译。在这里，我们报告存在的替代机制，Paip 2抑制翻译与eIF 4G竞争结合PABP。我们证明Paip 2可以消除PABP的翻译活性，PABP被拴在mRNA的3'末端。因此，Paip 2可以通过以前未被认识的机制抑制翻译，这与其破坏PABP-poly（A）相互作用的能力无关。
The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated by the cap-binding protein eIF4E, the poly(A) binding protein (PABP), and eIF4G, a scaffolding protein that bridges between ORE and PABP to bring about the circularization of the mRNA. The translational repressor, Paip2 (PABP-interacting protein 2), inhibits translation by promoting the dissociation of PABP from poly(A). Here we report on the existence of an alternative mechanism by which Paip2 inhibits translation by competing with eIF4G for binding to PABP. We demonstrate that Paip2 can abrogate the translational activity of PABP, which is tethered to the 3' end of the mRNA. Thus, Paip2 can inhibit translation by a previously unrecognized mechanism, which is independent of its ability to disrupt PABP-poly(A) interaction.