The RNA-binding protein caper is required for sensory neuron development in Drosophila melanogaster.

The RNA-binding protein caper is required for sensory neuron development in Drosophila melanogaster.
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DOI:
10.1002/dvdy.24523
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发表时间:
2017-08
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Lybecker MC
Lybecker MC
中科院分区:
其他
文献类型:
--
作者:
Olesnicky EC;Bono JM;Bell L;Schachtner LT;Lybecker MC

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由RNA结合蛋白(RNAbindingProteins,RBPs)介导的选择性剪接是基因表达调控的基本机制。选择性剪接已被证明是一种广泛的现象,它以组织特异性的方式促进基因产物的多样化。尽管选择性剪接缺陷源于许多神经疾病,但只有一小部分剪接因子得到了详细的研究。我们发现剪接因子Caper在果蝇多个生命阶段的多种不同的机械感觉神经元亚型的发育中是必需的。Caper功能的破坏会导致幼虫树突状突起神经元的树突形态发生、胚胎本体感受器的神经元定位以及成体机械感觉刷毛的发育和维持方面的缺陷。此外,我们发现Caper功能障碍会导致成年果蝇异常的运动行为。转录组范围的分析进一步支持了Caper在神经发生功能基因的替代异构体调控中的作用。我们的结果首次证明了在神经系统的发育和维持中对高度保守的剪接因子Caper的基本和广泛的需求,并为未来研究Caper介导的RNA调节的详细机制提供了一个框架。
Alternative splicing mediated by RNA-binding proteins (RBPs) is emerging as a fundamental mechanism for the regulation of gene expression. Alternative splicing has been shown to be a widespread phenomenon that facilitates the diversification of gene products in a tissue specific manner. Although defects in alternative splicing are rooted in many neurological disorders, only a small fraction of splicing factors have been investigated in detail. We find that the splicing factor Caper is required for the development of multiple different mechanosensory neuron subtypes at multiple life stages in Drosophila melanogaster. Disruption of Caper function causes defects in dendrite morphogenesis of larval dendrite arborization neurons, neuronal positioning of embryonic proprioceptors, as well as the development and maintenance of adult mechanosensory bristles. Additionally, we find that Caper dysfunction results in aberrant locomotor behavior in adult flies. Transcriptome-wide analyses further support a role for Caper in alternative isoform regulation of genes that function in neurogenesis. Our results provide the first evidence for a fundamental and broad requirement for the highly conserved splicing factor Caper in the development and maintenance of the nervous system and provide a framework for future studies on the detailed mechanism of Caper mediated RNA regulation.
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