在自闭症大脑中,神经元微电子的高度保守的程序被错误调节
Manuel Irimia1, Robert J Weatheritt2, Jonathan D Ellis3
1Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG), 88 Dr. Aiguader, Barcelona 08003, Spain.
Cell
|December 20, 2014
概括
替代拼接,特别是神经微子,对于大脑发育和蛋白质相互作用至关重要. 这些微子子的调节错误与自闭症谱系障碍有关.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 替代拼接 (AS) 产生了多样化的蛋白质,但其功能意义尚不清楚.
- 了解神经特异性AS对于神经发育研究至关重要.
研究的目的:
- 在哺乳动物中识别和描述功能协调,神经调节的AS事件.
- 调查微外电子在神经发生的作用及其与自闭症的联系.
主要方法:
- 对哺乳动物转录基因数据的分析,以确定AS程序.
- 通过神经元剪接因子nSR100/SRRM4.4研究微外子的调节.
- 在典型的神经发生与自闭症谱系障碍大脑中比较microexon调节.
主要成果:
- 确定了哺乳动物中最大的功能协调,神经调节的AS程序.
- 发现3-15个核酸微电子具有高度保护性和开关式调节性.
- 证明神经微外显子调节神经发生过程中至关重要的蛋白相互作用领域.
- 在自闭症谱系障碍大脑中发现了频繁的微电子调节错误,与降低的nSR100水平有关.
结论:
- 在神经发生过程中,一个微埃克森调节的保存程序重塑了蛋白质相互作用网络.
- 神经微电子的错误调节与自闭症谱系障碍有关.
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