Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Mol Cell. 2012 Jan 27;45(2):244-54. doi: 10.1016/j.molcel.2011.11.026.
The formation of mRNPs controls the interaction of the translation and degradation machinery with individual mRNAs. The yeast Scd6 protein and its orthologs regulate translation and mRNA degradation in yeast, C. elegans, D. melanogaster, and humans by an unknown mechanism. We demonstrate that Scd6 represses translation by binding the eIF4G subunit of eIF4F in a manner dependent on its RGG domain, thereby forming an mRNP repressed for translation initiation. Strikingly, several other RGG domain-containing proteins in yeast copurify with eIF4E/G and we demonstrate that two such proteins, Npl3 and Sbp1, also directly bind eIF4G and repress translation in a manner dependent on their RGG motifs. These observations identify the mechanism of Scd6 function through its RGG motif and indicate that eIF4G plays an important role as a scaffolding protein for the recruitment of translation repressors.
mRNPs 的形成控制着翻译和降解机制与单个 mRNA 的相互作用。酵母 Scd6 蛋白及其同源物通过未知机制在酵母、秀丽隐杆线虫、果蝇和人类中调节翻译和 mRNA 降解。我们证明 Scd6 通过其 RGG 结构域与 eIF4F 的 eIF4G 亚基结合来抑制翻译，从而形成一种对翻译起始有抑制作用的 mRNP。引人注目的是，酵母中其他几种含有 RGG 结构域的蛋白质与 eIF4E/G 共纯化，我们证明其中两种蛋白质 Npl3 和 Sbp1 也直接结合 eIF4G，并以依赖其 RGG 基序的方式抑制翻译。这些观察结果确定了 Scd6 通过其 RGG 基序发挥功能的机制，并表明 eIF4G 作为招募翻译抑制剂的支架蛋白发挥着重要作用。
