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首页> 外文期刊>Journal of Molecular Biology >Molecular Regulation of Alternative Polyadenylation (APA) within the Drosophila Nervous System
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Molecular Regulation of Alternative Polyadenylation (APA) within the Drosophila Nervous System

机译：果蝇神经系统内替代多腺苷酸化（APA）的分子调节

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Abstract Alternative polyadenylation (APA) is a widespread gene regulatory mechanism that generates mRNAs with different 3′-ends, allowing them to interact with different sets of RNA regulators such as microRNAs and RNA-binding proteins. Recent studies have shown that during development, neural tissues produce mRNAs with particularly long 3′UTRs, suggesting that such extensions might be important for neural development and function. Despite this, the mechanisms underlying neural APA are not well understood. Here, we investigate this problem within the Drosophila nervous system, focusing on the roles played by general cleavage and polyadenylation factors (CPA factors). In particular, we examine the model that modulations in CPA factor concentration may affect APA during development. For this, we first analyse the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression decreases during embryogenesis. In contrast to this global developmental decrease in CPA factor expression, we see that cleavage factor I (CFI) expression is actually elevated in the late embryonic central nervous system, suggesting that CFI might play a special role in neural tissues. To test this, we use the UAS/Gal4 system to deplete CFI proteins from neural tissue and observe that in this condition, multiple genes switch their APA patterns, demonstrating a role of CFI in APA control during Drosophila neural development. Furthermore, analysis of genes with 3′UTR extensions of different length leads us to suggest a novel relation between 3′UTR length and sensitivity to CPA factor expression. Our work thus contributes to the understanding of the mechanisms of APA control within the developing central nervous system. Graphical Abstract Display Omitted Highlights ? We study the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression overall decreases during embryogenesis. ? In contrast, we observe an increase in the expression of the CFI factors CFI25 and CFI68 in the Drosophila embryonic nervous system. ? We demonstrate a functional role of CFI expression on APA control during neural development in vivo .
机译：摘要替代的多腺苷酸化（APA）是一种广泛的基因调节机制，其产生具有不同的3'末端的MRNA，使它们与不同的RNA调节剂如MicroRNA和RNA结合蛋白相互作用。最近的研究表明，在发育过程中，神经组织具有特别长的3'UTR的MRNA，表明这种延伸对于神经发育和功能可能是重要的。尽管如此，神经APA的机制尚不清楚。在这里，我们研究了果蝇神经系统内的这个问题，重点关注一般裂解和多腺苷酸化因子（CPA因子）发挥的角色。特别是，我们检查CPA因子浓度的调制可能影响开发期间的APA模型。为此，我们首先分析所有哺乳动物CPA因子的果蝇原理表达，并注意其表达在胚胎发生期间降低。与CPA因子表达的这种全球发育减少相比，我们看到切割因子I（CFI）表达实际上在晚期胚胎中枢神经系统中升高，表明CFI可能在神经组织中发挥特殊作用。为了测试这一点，我们使用UAS / GAL4系统从神经组织中耗尽CFI蛋白并观察到在这种情况下，多种基因切换它们的APA模式，证明CFI在果蝇神经发育期间的APA控制的作用。此外，对不同长度的3'UR延伸的基因分析，我们建议3'UTR长度与对CPA因子表达的敏感性之间的新关系。因此，我们的工作有助于了解在发展中枢神经系统中的APA控制机制。图形抽象显示省略了亮点？我们研究了所有哺乳动物CPA因素的果蝇原理表达，并注意到它们在胚胎发生期间的表达总体降低。还是相比之下，我们观察CFI因子CFI25和CFI68在果蝇胚胎神经系统中表达的增加。还是我们证明了CFI表达在体内神经发育期间APA控制的功能作用。

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