hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies.
hnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies.
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DOI：
10.1038/nsmb.1815
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发表时间：
2010-06
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
淀粉样前体蛋白 (APP) 调节神经元突触功能，其裂解产物 Aβ 与阿尔茨海默病有关。在这里，我们提出的证据表明，RNA 结合蛋白 (RBP)、异质核核糖核蛋白 (hnRNP) C 和脆性 X 智力低下蛋白 (FMRP) 与相同的 APP mRNA 编码区元件相关，并以相反的方向竞争性地影响 APP 翻译。沉默 hnRNP C 会增加 FMRP 与 APP mRNA 的结合并抑制 APP 翻译，而沉默 FMRP 则会增强 hnRNP C 结合并促进翻译。 APP 翻译的抑制与 FMRP 和标记的 APP mRNA 在加工体 (PB) 内的共定位有关；这种共定位被 hnRNP C 过表达或 FMRP 沉默所消除。我们的研究结果表明，FMRP 通过将 APP mRNA 招募到 PB 来抑制翻译，而 hnRNP C 通过取代 FMRP 来促进 APP 翻译，从而缓解翻译障碍。
Amyloid precursor protein (APP) regulates neuronal synapse function and its cleavage product Aβ is linked to Alzheimer’s disease. Here, we present evidence that RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile-X mental retardation protein (FMRP) associate with the same APP mRNA coding region element and influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, while silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP mRNA within processing bodies (PBs); this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to PBs, while hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.
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影响因子：
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