Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation
Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation
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DOI：
10.1101/gad.505709
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发表时间：
2009-01-15
影响因子：
10.5
通讯作者：
Ephrussi, Anne
中科院分区：
文献类型：
--
作者：
Besse, Florence;de Quinto, Sonia Lopez;Ephrussi, Anne
不对称富集的mRNA的局部翻译是细胞功能极化的有力机制。在果蝇中，Oskar蛋白在卵母细胞后极的专门积累对于未来胚胎的发育至关重要。这是通过形成一个动态的奥斯卡核糖核蛋白（RNP）复合物调节奥斯卡mRNA的运输，其翻译抑制，而非本地化，并在到达后极后，其翻译激活。我们鉴定了核质穿梭蛋白PTB（polypyrimidine tract-binding protein）/hnRNP I作为体内与oskar RNP相关的新因子。虽然PTB的功能在很大程度上依赖于oskar mRNA的转运，但它对定位mRNA的翻译抑制是必要的。出乎意料的是，PTB的细胞质形式可以与oskar mRNA结合并抑制其翻译，这表明PTB向oskar复合物的核募集对于其调节功能不是必需的。此外，PTB直接结合到沿着oskar 39非翻译区的多个位点，并介导含有多个oskar RNA分子的高阶复合物在体内的组装。因此，PTB是奥斯卡RNP复合物的关键结构组分，其双重控制高阶RNP颗粒的形成和翻译沉默。
Local translation of asymmetrically enriched mRNAs is a powerful mechanism for functional polarization of the cell. In Drosophila, exclusive accumulation of Oskar protein at the posterior pole of the oocyte is essential for development of the future embryo. This is achieved by the formation of a dynamic oskar ribonucleoprotein (RNP) complex regulating the transport of oskar mRNA, its translational repression while unlocalized, and its translational activation upon arrival at the posterior pole. We identified the nucleo-cytoplasmic shuttling protein PTB ( polypyrimidine tract-binding protein)/hnRNP I as a new factor associating with the oskar RNP in vivo. While PTB function is largely dispensable for oskar mRNA transport, it is necessary for translational repression of the localizing mRNA. Unexpectedly, a cytoplasmic form of PTB can associate with oskar mRNA and repress its translation, suggesting that nuclear recruitment of PTB to oskar complexes is not required for its regulatory function. Furthermore, PTB binds directly to multiple sites along the oskar 39 untranslated region and mediates assembly of high-order complexes containing multiple oskar RNA molecules in vivo. Thus, PTB is a key structural component of oskar RNP complexes that dually controls formation of high-order RNP particles and translational silencing.