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首页> 外文期刊>Molecular and Cellular Biology >Homologues of the Caenorhabditis elegans Fox-1 Protein Are Neuronal Splicing Regulators in Mammals
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Homologues of the Caenorhabditis elegans Fox-1 Protein Are Neuronal Splicing Regulators in Mammals

机译：秀丽隐杆线虫Fox-1蛋白的同系物是哺乳动物中的神经元剪接调节剂。

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A vertebrate homologue of the Fox-1 protein from C. elegans was recently shown to bind to the element GCAUG and to act as an inhibitor of alternative splicing patterns in muscle. The element UGCAUG is a splicing enhancer element found downstream of numerous neuron-specific exons. We show here that mouse Fox-1 (mFox-1) and another homologue, Fox-2, are both specifically expressed in neurons in addition to muscle and heart. The mammalian Fox genes are very complex transcription units that generate transcripts from multiple promoters and with multiple internal exons whose inclusion is regulated. These genes produce a large family of proteins with variable N and C termini and internal deletions. We show that the overexpression of both Fox-1 and Fox-2 isoforms specifically activates splicing of neuronally regulated exons. This splicing activation requires UGCAUG enhancer elements. Conversely, RNA interference-mediated knockdown of Fox protein expression inhibits splicing of UGCAUG-dependent exons. These experiments show that this large family of proteins regulates splicing in the nervous system. They do this through a splicing enhancer function, in addition to their apparent negative effects on splicing in vertebrate muscle and in worms.
机译：来自 C的Fox-1蛋白的脊椎动物同源物。线虫最近被证明与GCAUG元素结合并可以抑制肌肉中的其他剪接模式。元件UGCAUG是在许多神经元特异性外显子下游发现的剪接增强元件。我们在这里显示，小鼠Fox-1（mFox-1）和另一个同系物Fox-2，除了肌肉和心脏外，均在神经元中特异性表达。哺乳动物的Fox基因是非常复杂的转录单位，可以从多个启动子生成转录物，并具有多个内部外显子，其内含子受到调节。这些基因产生具有可变N和C末端以及内部缺失的蛋白质家族。我们表明，Fox-1和Fox-2亚型的过表达特别激活了神经调节外显子的剪接。此拼接激活需要UGCAUG增强器元素。相反，RNA干扰介导的敲除Fox蛋白表达抑制了UGCAUG依赖外显子的剪接。这些实验表明，这个庞大的蛋白质家族调节着神经系统中的剪接。它们除了对脊椎动物肌肉和蠕虫中的剪接产生明显的负面影响外，还通过剪接增强剂功能来实现此目的。

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