Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.
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Pumilio,Nanos和脑肿瘤蛋白对Messenger RNA的组合控制。

DOI:
10.1080/15476286.2017.1306168
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发表时间:
2017-11-02
期刊:
影响因子:
4.1
通讯作者:
Goldstrohm AC
Goldstrohm AC
中科院分区:
生物学3区
文献类型:
--
作者:
Arvola RM;Weidmann CA;Tanaka Hall TM;Goldstrohm AC

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真核生物拥有大量的RNA结合蛋白(RBP),它们以不同的方式影响mRNA以控制蛋白质表达。RBP对mRNA的组合调控正逐渐成为一种规律。没有任何例子能像3种果蝇RBP、Pumilio、Nanos和脑瘤的伙伴关系那样生动地说明这一点,它们在发育、干细胞维持和分化、生育和神经过程中具有重叠的功能。在这里,我们综合了30年的研究,对它们的分子功能和作用机制有了新的认识。首先,我们提供每个RBP的关键属性的概述。接下来,我们提出了一个详细的分析,他们的合作监管机制,使用一个典型的例子,发育形态,驼背,这是空间和时间上的三人在胚胎发育过程中调节。新的生物化学、结构和功能分析为RNA识别、协同性和调控机制提供了新的见解。我们将这些数据整合到一个模型中的组合RNA结合和调节翻译和mRNA衰变。然后,我们使用这些信息,转录组范围的分析和生物信息学预测来评估Pumilio,Nanos和脑瘤对基因调控的全球影响。总之,结果支持普遍的,动态的转录后控制。
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.
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