The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex
The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex
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DOI：
10.1101/gad.1170204
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发表时间：
2004-04-01
影响因子：
10.5
通讯作者：
Maquat, LE
中科院分区：
文献类型：
--
作者：
Chin, SY;Lejeune, F;Maquat, LE
大部分细胞蛋白来源于真核翻译起始因子（eIF） 4e结合mRNA的翻译。然而，最近对无义介导的mRNA衰变（NMD）的研究表明，帽结合蛋白（CBP）80结合的mRNA是eif4e结合mRNA的前体，也可以在翻译的先驱轮中被翻译。在这里，我们报告了可以通过测量NMD来评估的先锋轮不受4E-BP1的抑制，已知4E-BP1通过与eIF4G竞争结合eIF4E来抑制稳态翻译。因此，至少在这一点上，先锋翻译与稳态翻译是有区别的。eIF4GI、聚(A)结合蛋白（PABP）1、eIF3、eIF4AI和eIF2alpha与CBP80和eIF4E共同免疫纯化，这表明每个因子在两种翻译模式中都起作用。与PABP1和eIF2alpha在翻译初期的作用一致，已知会破坏PABP1与poly(A)结合并抑制稳态翻译的pabp -相互作用蛋白2，以及已知会抑制稳态翻译的非活性eIF2alpha也会抑制NMD。多体谱表明，cbp80结合的mrna的翻译效率低于eif4e结合的mrna。
The bulk of cellular proteins derive from the translation of eukaryotic translation initiation factor (eIF)4E-bound mRNA. However, recent studies of nonsense-mediated mRNA decay (NMD) indicate that cap-binding protein (CBP)80-bound mRNA, which is a precursor to eIF4E-bound mRNA, can also be translated during a pioneer round of translation. Here, we report that the pioneer round, which can be assessed by measuring NMD, is not inhibited by 4E-BP1, which is known to inhibit steady-state translation by competing with eIF4G for binding to eIF4E. Therefore, at least in this way, the pioneer round of translation is distinct from steady-state translation. eIF4GI, poly(A)-binding protein (PABP)1, eIF3, eIF4AI, and eIF2alpha coimmunopurify with both CBP80 and eIF4E, which suggests that each factor functions in both modes of translation. Consistent with roles for PABP1 and eIF2alpha in the pioneer round of translation, PABP-interacting protein 2, which is known to destabilize PABP1 binding to poly(A) and inhibit steady-state translation, as well as inactive eIF2alpha, which is also known to inhibit steady-state translation, also inhibit NMD. Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts.