The identification of protein and RNA interactors of the splicing factor Caper in the adult Drosophila nervous system.

The identification of protein and RNA interactors of the splicing factor Caper in the adult Drosophila nervous system.
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DOI:
10.3389/fnmol.2023.1114857
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发表时间:
2023
影响因子:
4.8
通讯作者:
Olesnicky, Eugenia C.
Olesnicky, Eugenia C.
中科院分区:
医学2区
文献类型:
--
作者:
Titus, M. Brandon;Chang, Adeline W.;Popitsch, Niko;Ebmeier, Christopher C.;Bono, Jeremy M.;Olesnicky, Eugenia C.

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转录后基因调控是帮助调节神经系统发育和健康衰老的基本机制。破坏 RNA 结合蛋白 (RBP) 功能的突变越来越多地与神经系统疾病有关,包括肌萎缩侧索硬化症、脆性 X 综合征和脊髓性肌萎缩症。有趣的是,尽管大多数 RBP 在不同的组织类型中广泛表达,但神经系统通常对其功能障碍特别敏感。因此,阐明普遍表达的 RBP 功能障碍导致的异常 RNA 调节如何导致神经系统疾病的组织特异性病理至关重要。高度保守的 RBP 和选择性剪接因子 Caper 在整个发育过程中广泛表达,是果蝇感觉和运动神经元发育所必需的。此外,刺山柑功能障碍导致幼虫和成虫的运动缺陷。尽管如此,我们对哪些蛋白质与 Caper 相互作用以及哪些 RNA 受 Caper 调节知之甚少。在这里,我们鉴定了神经组织和肌肉组织中与 Caper 相互作用的蛋白质,以及神经特异性 Caper 靶 RNA。此外,我们发现这些刺山柑相互作用蛋白和 RNA 的一个子集与刺山柑发生遗传相互作用,以调节果蝇的重力行为。
Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly, although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often particularly sensitive to their dysfunction. It is therefore critical to elucidate how aberrant RNA regulation that results from the dysfunction of ubiquitously expressed RBPs leads to tissue specific pathologies that underlie neurological diseases. The highly conserved RBP and alternative splicing factor Caper is widely expressed throughout development and is required for the development of Drosophila sensory and motor neurons. Furthermore, caper dysfunction results in larval and adult locomotor deficits. Nonetheless, little is known about which proteins interact with Caper, and which RNAs are regulated by Caper. Here we identify proteins that interact with Caper in both neural and muscle tissue, along with neural specific Caper target RNAs. Furthermore, we show that a subset of these Caper-interacting proteins and RNAs genetically interact with caper to regulate Drosophila gravitaxis behavior.
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