Department of Life Sciences, Pohang University of Science and Technology, Nam-gu, Pohang 37673, Republic of Korea.
School of Interdisciplinary Bioscience & Bioengineering, Pohang University of Science and Technology, Nam-gu, Pohang 37673, Republic of Korea.
Nucleic Acids Res. 2022 Jan 11;50(1):306-321. doi: 10.1093/nar/gkab1205.
Poly(A)-binding protein (PABP) is a translation initiation factor that interacts with the poly(A) tail of mRNAs. PABP bound to poly(A) stimulates translation by interacting with the eukaryotic initiation factor 4G (eIF4G), which brings the 3' end of an mRNA close to its 5' m7G cap structure through consecutive interactions of the 3'-poly(A)-PABP-eIF4G-eIF4E-5' m7G cap. PABP is a highly abundant translation factor present in considerably larger quantities than mRNA and eIF4G in cells. However, it has not been elucidated how eIF4G, present in limited cellular concentrations, is not sequestered by mRNA-free PABP, present at high cellular concentrations, but associates with PABP complexed with the poly(A) tail of an mRNA. Here, we report that RNA-free PABPs dimerize with a head-to-head type configuration of PABP, which interferes in the interaction between PABP and eIF4G. We identified the domains of PABP responsible for PABP-PABP interaction. Poly(A) RNA was shown to convert the PABP-PABP complex into a poly(A)-PABP complex, with a head-to-tail-type configuration of PABP that facilitates the interaction between PABP and eIF4G. Lastly, we showed that the transition from the PABP dimer to the poly(A)-PABP complex is necessary for the translational activation function.
聚腺苷酸化结合蛋白(PABP)是一种翻译起始因子,可与 mRNA 的 poly(A) 尾巴相互作用。与 poly(A) 结合的 PABP 通过与真核起始因子 4G(eIF4G)相互作用来刺激翻译,eIF4G 通过 poly(A)-PABP-eIF4G-eIF4E-5' m7G 帽结构的连续相互作用,使 mRNA 的 3' 端靠近其 5' m7G 帽结构。PABP 是一种高度丰富的翻译因子,在细胞中的含量远高于 mRNA 和 eIF4G。然而,目前还不清楚为什么在细胞中浓度有限的 eIF4G 不会被高细胞浓度下存在的无 mRNA 的 PABP 隔离,而是与与 mRNA 的 poly(A) 尾巴结合的 PABP 相关联。在这里,我们报告说无 RNA 的 PABP 以 PABP 头对头的类型构型二聚化,这会干扰 PABP 和 eIF4G 之间的相互作用。我们确定了 PABP 负责 PABP-PABP 相互作用的结构域。poly(A) RNA 显示出将 PABP-PABP 复合物转化为具有 PABP 头到尾类型构型的 poly(A)-PABP 复合物,这有利于 PABP 和 eIF4G 之间的相互作用。最后,我们表明从 PABP 二聚体到 poly(A)-PABP 复合物的转变是翻译激活功能所必需的。