The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.
The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.
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DOI：
10.1016/j.celrep.2017.03.022
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发表时间：
2017-04-04
期刊：
影响因子：
8.8
通讯作者：
Gavis ER
中科院分区：
文献类型：
--
作者：
Tamayo JV;Teramoto T;Chatterjee S;Hall TMT;Gavis ER
果蝇hnRNP F/H同源物Glorund（Glo）通过与nanos 3′非翻译区中富含UA的结构化基序相互作用来调节nanos mRNA的翻译。然而，Glo调节另外的RNA，并且哺乳动物同源物结合G-tract序列以调节选择性剪接，这表明Glo也识别G-tract RNA。为了深入了解Glo如何识别结构化的富含UA和G-tract RNA，我们使用了由Glo RNA结合结构域的晶体结构指导的突变分析，并确定了两个离散的RNA结合表面，使Glo能够识别两种RNA基序。通过工程Glo的变体，有利于一个单一的RNA结合模式，我们表明，一个子集的Glo的功能在体内介导的G-道结合模式，而纳米调控需要两种识别模式。我们的研究结果表明，在Glo的双重RNA基序识别的进化的分子机制，可适用于了解其他RNA结合蛋白的功能多样性。
The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3′ untranslated region. Glo regulates additional RNAs however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.