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首页> 外文期刊>Neuron >Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons Regulates Cortical Development and Cerebellar Function
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Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons Regulates Cortical Development and Cerebellar Function

机译：肠兴奋性和抑制性神经元中的差异Nova2介导的剪接调节皮质发育和小脑功能

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摘要

RNA-binding proteins (RBPs) regulate genetic diversity, but the degree to which they do so in individual cell types in vivo is unknown. We developed NOVA2 cTag-crosslinking and immunoprecipitation (CLIP) to generate functional RBP-RNA maps from different neuronal populations in the mouse brain. Combining cell type datasets from Nova2-cTag and Nova2 conditional knockout mice revealed differential NOVA2 regulatory actions on alternative splicing (AS) on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons, where we find NOVA2 is required for, respectively, development of laminar structure, motor coordination, and synapse formation. We also find that NOVA2-regulated AS is coupled to NOVA2 regulation of intron retention in hundreds of transcripts, which can sequester the trans-acting splicing factor PTBP2. In summary, cTag-CLIP complements single-cell RNA sequencing (RNA-seq) studies by providing a means for understanding RNA regulation of functional cell diversity.
机译：RNA结合蛋白（RBPS）调节遗传多样性，但它们在体内单个细胞类型中所做的程度是未知的。我们开发了Nova2 CTAG交联和免疫沉淀（夹子）以产生来自小鼠脑中不同神经元群的功能性RBP-RNA图。组合来自Nova2-CTAG和Nova2条件敲除小鼠的细胞类型数据集显示了在不同神经元表达的相同转录中的替代剪接（AS）上的差异Nova2调节作用。这包括在皮质和小脑兴奋性与抑制性神经元中表达的转录物中的功能差异，在其中寻找Nova2，分别是开发层状结构，电动机协调和突触形成。我们还发现Nova2-调节的偶联与数百种转录物中的内含子保留的Nova2调节，这可以螯合反式作用剪接因子PTBP2。总之，CTAG-CLIP通过提供用于理解功能细胞多样性的RNA调节的方法来补充单细胞RNA测序（RNA-SEQ）研究。

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  • 来源
    《Neuron》 |2019年第4期|共19页
  • 作者

    Saito Yuhki; Yuan Yuan; Zucker-Scharff Ilana; Fak John J.; Jereb Sasa; Tajima Yoko; Licatalosi Donny D.; Darnell Robert B.;

  • 作者单位

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

    Case Western Reserve Univ Ctr RNA Sci &

    Therapeut Cleveland OH 44106 USA;

    Rockefeller Univ Lab Mol Neurooncol 1230 York Ave New York NY 10065 USA;

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  • 正文语种 eng
  • 中图分类 神经病学;
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