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首页> 美国卫生研究院文献>Genetics >Divergent Functions Through Alternative Splicing: The DrosophilaCRMP Gene in Pyrimidine Metabolism Brain and Behavior
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Divergent Functions Through Alternative Splicing: The DrosophilaCRMP Gene in Pyrimidine Metabolism Brain and Behavior

机译：通过选择性剪接实现不同功能：果蝇嘧啶代谢大脑和行为中的CRMP基因

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摘要

DHP and CRMP proteins comprise a family of structurally similar proteins that perform divergent functions, DHP in pyrimidine catabolism in most organisms and CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP proteins are products of six genes; however, Drosophila melanogaster has a single gene that encodes one DHP and one CRMP protein through tissue-specific, alternative splicing of a pair of paralogous exons. The proteins derived from the fly gene are identical over 90% of their lengths, suggesting that unique, novel functions of these proteins derive from the segment corresponding to the paralogous exons. Functional homologies of the Drosophila and mammalian CRMP proteins are revealed by several types of evidence. Loss-of-function mutation modifies both Ras and Rac misexpression phenotypes during fly eye development in a manner that is consistent with the roles of CRMP in Ras and Rac signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation impairs learning and memory. CRMP mutant flies are defective in circadian activity rhythm. Thus, DHP and CRMP proteins are derived by different processes in flies (tissue-specific, alternative splicing of paralogous exons of a single gene) and vertebrates (tissue-specific expression of different genes), indicating that diverse genetic mechanisms have mediated the evolution of this protein family in animals.
机译：DHP和CRMP蛋白质包含一系列结构相似的蛋白质，它们执行不同的功能，DHP在大多数生物体中的嘧啶分解代谢中，而CRMP在动物的神经元动力学中。在脊椎动物中，一种DHP和5种CRMP蛋白是6种基因的产物。然而，果蝇具有一个单一基因，该基因通过组织特异性，一对旁源外显子的可变剪接编码一个DHP和一个CRMP蛋白。从果蝇基因衍生的蛋白质在其90％的长度上都是相同的，这表明这些蛋白质独特，新颖的功能源自与旁系外显子相对应的片段。果蝇和哺乳动物CRMP蛋白的功能同源性通过多种类型的证据得以揭示。功能丧失突变以与CRMP在哺乳动物神经元Ras和Rac信号通路中的作用相一致的方式，在蝇眼发育过程中修饰了Ras和Rac错误表达表型。在小鼠和果蝇中，CRMP突变都会损害学习和记忆。 CRMP突变体果蝇的昼夜活动节律有缺陷。因此，DHP和CRMP蛋白是通过不同的过程在果蝇（组织特异性，单个基因的旁系外显子的选择性剪接）和脊椎动物（不同基因的组织特异性表达）中衍生的，这表明多种遗传机制已经介导了海马的进化。动物中的这种蛋白质家族。

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