Alternative Splicing in Neurogenesis and Brain Development.
Alternative Splicing in Neurogenesis and Brain Development.
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DOI：
10.3389/fmolb.2018.00012
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发表时间：
2018
影响因子：
5
通讯作者：
Tarn WY
中科院分区：
文献类型：
--
作者：
Su CH;D D;Tarn WY
前体mRNA的选择性剪接是增加转录组和蛋白质组多样性并在转录后调节mRNA水平的重要机制。选择性剪接在脑组织中以高频率发生，并有助于神经系统发育的每一步，包括细胞命运决定、神经元迁移、轴突引导和突触发生。遗传操作和RNA测序提供了深入了解的干细胞自我更新和神经元命运规范的选择性剪接的影响的分子机制。神经元特异性剪接调节因子的及时表达和可能的翻译后修饰在神经元发育中起重要作用。许多关键转录调节因子或表观遗传因子的选择性剪接重新编程转录组，因此有助于干细胞命运的决定。在神经元分化过程中，选择性剪接还调节信号传导活性、中心粒动力学和代谢途径。此外，选择性剪接影响皮质分层和神经元发育和功能。在这篇综述中，我们专注于了解选择性剪接对神经发生和大脑发育的贡献，这揭示了剪接缺陷如何导致大脑疾病和疾病的最新进展。
Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.