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成年神经系统中剪接因子Caper的蛋白质和RNA相互作用分子的鉴定。

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

作者信息

Titus M Brandon, Chang Adeline W, Popitsch Niko, Ebmeier Christopher C, Bono Jeremy M, Olesnicky Eugenia C

机构信息

Department of Biology, University of Colorado Colorado Springs, Colorado Springs, CO, United States.

Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Vienna, Austria.

出版信息

Front Mol Neurosci. 2023 Jun 23;16:1114857. doi: 10.3389/fnmol.2023.1114857. eCollection 2023.

Abstract

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 sensory and motor neurons. Furthermore, 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 to regulate gravitaxis behavior.

摘要

转录后基因调控是一种基本机制,有助于调节神经系统的发育和健康衰老。破坏RNA结合蛋白(RBPs)功能的突变与包括肌萎缩侧索硬化症、脆性X综合征和脊髓性肌萎缩症在内的神经疾病越来越相关,这些蛋白负责调控转录后基因表达。有趣的是,尽管大多数RBPs在多种组织类型中广泛表达,但神经系统通常对它们的功能障碍特别敏感。因此,阐明普遍表达的RBPs功能障碍导致的异常RNA调控如何导致构成神经疾病基础的组织特异性病变至关重要。高度保守的RBP和可变剪接因子Caper在整个发育过程中广泛表达,是感觉和运动神经元发育所必需的。此外,功能障碍会导致幼虫和成虫的运动缺陷。然而,关于哪些蛋白质与Caper相互作用,以及哪些RNA受Caper调控,我们知之甚少。在这里,我们鉴定了在神经和肌肉组织中与Caper相互作用的蛋白质,以及神经特异性Caper靶RNA。此外,我们表明,这些与Caper相互作用的蛋白质和RNA的一个子集在基因上相互作用以调节趋地性行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a06/10332324/2eb49e740b61/fnmol-16-1114857-g001.jpg

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