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Conserved Alternative Splicing and Expression Patterns of Arthropod N-Cadherin

机译：节肢动物N-Cadherin的保守替代拼接和表达模式

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Metazoan development requires complex mechanisms to generate cells with diverse function. Alternative splicing of pre-mRNA not only expands proteomic diversity but also provides a means to regulate tissue-specific molecular expression. The N-Cadherin gene in Drosophila contains three pairs of mutually-exclusive alternatively-spliced exons (MEs). However, no significant differences among the resulting protein isoforms have been successfully demonstrated in vivo. Furthermore, while the N-Cadherin gene products exhibit a complex spatiotemporal expression pattern within embryos, its underlying mechanisms and significance remain unknown. Here, we present results that suggest a critical role for alternative splicing in producing a crucial and reproducible complexity in the expression pattern of arthropod N-Cadherin. We demonstrate that the arthropod N-Cadherin gene has maintained the three sets of MEs for over 400 million years using in silico and in vivo approaches. Expression of isoforms derived from these MEs receives precise spatiotemporal control critical during development. Both Drosophila and Tribolium use ME-13a and ME-13b in “neural” and “mesodermal” splice variants, respectively. As proteins, either ME-13a- or ME-13b-containing isoform can cell-autonomously rescue the embryonic lethality caused by genetic loss of N-Cadherin. Ectopic muscle expression of either isoform beyond the time it normally ceases leads to paralysis and lethality. Together, our results offer an example of well-conserved alternative splicing increasing cellular diversity in metazoans.
机译：Metazoan开发需要复杂的机制来产生具有多样化功能的细胞。前mRNA的替代剪接不仅扩大蛋白质组学多样性，还提供了调节组织特异性分子表达的方法。果蝇中的n-cadherin基因含有三对相互关联的交替剪接外显子（MES）。然而，在体内成功证明了所得蛋白质同种型中没有显着差异。此外，虽然n-cadherin基因产物在胚胎内表现出复杂的时空表达模式，但其潜在的机制和意义仍然是未知的。在这里，我们提出了替代剪接在节肢动物N-钙粘蛋白的表达模式中产生关键和可重复的复杂性的替代剪接的关键作用。我们表明，在硅和体内方法中，节肢动物N-Cadherin基因在4亿多年中保持了三组MES超过4亿年。来自这些MES的同种型的表达在开发期间接受了临界临界的精确的时空控制。果蝇和肮脏的既分别都在“神经”和“中胚层”剪接变体中使用ME-13A和ME-13B。作为蛋白质，可以细胞 - 含有ME-13A-或ME-13B的同种型可以细胞 - 自主拯救由N-cadherin的遗传丧失引起的胚胎致死性。异位肌肉表达无论是在通常停止的时间内的同种型导致瘫痪和致死性。我们的结果在一起提供了一个稳定的替代拼接的例子，增加了美唑烷的细胞多样性。

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