在发育中的新皮层中,通过Rbfox1/2/3进行转录调节器和Ptbp1的细胞类型特定剪接
Xiangbin Ruan1,2, Kaining Hu1,2, Yalan Yang1,2
1Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA.
bioRxiv : the preprint server for biology
|September 24, 2024
概括
主拼接调节器和转录因子在发育中的大脑中表现出差异拼接. 这项研究揭示了Rbfox蛋白如何影响拼接,影响神经元发育和细胞迁移.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 发育中的大脑中替代拼接的复杂机制,特别是关于转录调节者的复杂机制,仍然不完全理解.
- 研究拼接调节器和转录因子之间的交叉声对解读神经发育期间细胞类型特定的基因表达至关重要.
研究的目的:
- 阐明主拼接调节器如何与转录调节器相互作用.
- 为了确定在新皮层发育中的转录调节器中差异拼接的程度.
- 了解神经元发育中改变拼接的功能后果.
主要方法:
- 细胞类型特定的RNA测序 (RNA-Seq) 的新皮质的发展.
- 在转录调节器中对替代拼接事件的分析.
- 功能性研究涉及Rbfox蛋白表达和剥离 (Rbfox1/2/3).
- 调查Meis2异形特异性功能的研究.
主要成果:
- 转录调节器在差异拼接方面得到显著丰富,导致蛋白质异型变化或无意义介导的mRNA衰变.
- 当Rbfox蛋白在辐射原体中短暂表达时,会诱导神经元剪接事件,特别是在Meis2和Tead1.1等转录调节器中.
- Rbfox 蛋白调节 Ptbp1 的剪接,包括一种哺乳动物特异性的外子和一种新的毒素外子.
- 在新皮层中Rbfox1/2/3的消去导致神经元异型的下调和辐射神经元迁移的受损.
- 不同的Meis2异型表现出不同的功能:原始异型促进Tgfb3转录,而神经元异型促进神经元分化.
结论:
- 转录调节器在发育中的新皮质中经历细胞类型之间的差异拼接.
- 像Rbfox蛋白质这样的拼接调节器在脑发育过程中在编排细胞类型特定的拼接程序方面发挥着关键作用.
- 转录因子的差异拼接有助于神经元的分化和迁移.
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