Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin β
Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin β
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DOI：
10.1101/gad.1817109
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发表时间：
2009-11-01
影响因子：
10.5
通讯作者：
Maquat, Lynne E.
中科院分区：
文献类型：
--
作者：
Sato, Hanae;Maquat, Lynne E.
哺乳动物mRNA在其整个生命周期中丢失和获得蛋白质，同时经历加工，运输，翻译和衰变。翻译如何影响信使RNA（mRNA）-蛋白质相互作用在很大程度上是未知的。第一轮翻译使用新合成的mRNA，该mRNA在帽处与帽结合蛋白80（CBP 80）-CBP 20（也称为帽结合复合物[CBC]）结合，在poly（A）尾处与poly（A）结合蛋白N1（PABPN 1）和PABPC 1结合，并且如果生物发生涉及前体mRNA剪接，则在外显子-外显子连接处与外显子连接复合物（EJC）结合。随后的几轮翻译涉及在帽处被真核翻译起始因子4 E（eIF 4 E）和在poly（A）尾处被PABPC 1结合的mRNA，但缺乏可检测的EJC和PABPN 1。使用细胞内铁的水平来调节特定mRNA的翻译，我们表明翻译不仅促进EJC成分的去除，包括eIF 4AIII锚，而且还通过PABPC 1替换PABPN 1。值得注意的是，翻译不影响eIF 4 E对CBC的替代。相反，输入蛋白β（IMP β）促进了eIF 4 E对CBC的替代：使用IMP α伊布（IMP β结合）结构域或RAN变体抑制IMP β与mRNA帽处CBC-IMP α复合物的结合，增加了CBC的量结合mRNA并减少了eIF 4 E结合mRNA的量。我们的研究揭示了IMP β以前未被重视的作用，以及新合成的信使核糖核蛋白（mRNP）如何成熟的新范式。
Mammalian mRNAs lose and acquire proteins throughout their life span while undergoing processing, transport, translation, and decay. How translation affects messenger RNA (mRNA)-protein interactions is largely unknown. The pioneer round of translation uses newly synthesized mRNA that is bound by cap-binding protein 80 (CBP80)-CBP20 (also known as the cap-binding complex [CBC]) at the cap, poly(A)-binding protein N1 (PABPN1) and PABPC1 at the poly(A) tail, and, provided biogenesis involves pre-mRNA splicing, exon junction complexes (EJCs) at exon-exon junctions. Subsequent rounds of translation engage mRNA that is bound by eukaryotic translation initiation factor 4E (eIF4E) at the cap and PABPC1 at the poly(A) tail, but that lacks detectable EJCs and PABPN1. Using the level of intracellular iron to regulate the translation of specific mRNAs, we show that translation promotes not only removal of EJC constituents, including the eIF4AIII anchor, but also replacement of PABPN1 by PABPC1. Remarkably, translation does not affect replacement of CBC by eIF4E. Instead, replacement of CBC by eIF4E is promoted by importin beta (IMP beta): Inhibiting the binding of IMP beta to the complex of CBC-IMP alpha at an mRNA cap using the IMP alpha IBB (IMP beta-binding) domain or a RAN variant increases the amount of CBC-bound mRNA and decreases the amount of eIF4E-bound mRNA. Our studies uncover a previously unappreciated role for IMP beta and a novel paradigm for how newly synthesized messenger ribonucleoproteins (mRNPs) are matured.