Karim Muhammad M, Svitkin Yuri V, Kahvejian Avak, De Crescenzo Gregory, Costa-Mattioli Mauro, Sonenberg Nahum
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, QC, Canada H3G 1Y6.
Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9494-9. doi: 10.1073/pnas.0603701103. Epub 2006 Jun 13.
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 eIF4E 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.
真核生物信使核糖核酸(mRNA)的3' 聚腺苷酸(poly(A))尾巴和5' 帽协同作用以增强翻译。这种相互作用由帽结合蛋白eIF4E、聚腺苷酸结合蛋白(PABP)和eIF4G介导,eIF4G是一种支架蛋白,它在eIF4E和PABP之间架桥,使mRNA环化。翻译抑制因子Paip2(PABP相互作用蛋白2)通过促进PABP与聚腺苷酸的解离来抑制翻译。在此我们报告存在一种替代机制,通过该机制Paip2通过与eIF4G竞争结合PABP来抑制翻译。我们证明Paip2可以消除与mRNA 3' 端相连的PABP的翻译活性。因此,Paip2可以通过一种以前未被认识的机制抑制翻译,该机制与其破坏PABP - 聚腺苷酸相互作用的能力无关。