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对等RNA结合蛋白的差异表达建立了正常大脑皮层发育所需的动态拼接程序

Eleonora Cesari^1,2, Donatella Farini^3,4, Vanessa Medici¹

¹Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy.

Nucleic acids research

|February 7, 2024

概括

Sam68和SLM2RNA结合蛋白 (RBPs) 通过动态拼接控制大脑发育. 它们对立的表达模式和冗余功能对于神经发生和生存能力至关重要.

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
发展生物学发展生物学

背景情况:

Sam68和SLM2是类似的RNA结合蛋白 (RBPs),在大脑皮层具有类似的拼接功能.
它们在皮层发育过程中的独特作用和调节相互作用在很大程度上仍未被描述.

研究的目的:

研究Sam68和SLM2在皮层发育中的相对功能.
阐明管理它们的表达模式和拼接活动的调节机制.

主要方法:

在小鼠皮层发育过程中分析Sam68和SLM2表达模式.
产生和分析Sam68:Slm2双淘汰赛 (Sam68:Slm2dko) 的小鼠.
在野生类型和淘汰皮层中进行外显子级拼接分析.

主要成果:

Sam68和SLM2表现出相反的发育表达模式,SLM2在层次上控制Sam68的表达.
Sam68和SLM2的联合耗尽影响了数百个外子,揭示了它们对拼接的联合影响.
受到SLM2调节的外子表现出动态拼接,而依赖Sam68的外子则被构成性拼接;在Sam68:Slm2dko小鼠中,这种动态模式被废除了.
Sam68:Slm2dko小鼠表现出患有神经发生和神经元分化缺陷的围产死亡率,以及与改变拼接相关的水头.

结论:

Sam68和SLM2的发育调节协调了一个动态拼接程序,这对大脑发育和生存至关重要.
这些相似的RBPs提供了一个强大的,冗余的机制,支持正确的皮质发育.
这项研究强调了协调RBP功能的关键作用,以确保正确的大脑形成和生存能力.

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