Robert J and Nancy D Carney Institute for Brain Science, Department of Neuroscience, Brown University, Providence, RI 02912, USA.
Robert J and Nancy D Carney Institute for Brain Science, Department of Neuroscience, Brown University, Providence, RI 02912, USA.
Curr Opin Neurobiol. 2019 Aug;57:26-31. doi: 10.1016/j.conb.2018.12.013. Epub 2019 Jan 28.
Dynamic changes in alternative splicing during the life cycle of neurons support development and plasticity, and are implicated in disease pathology. Cell-specific alternative splicing programs coordinate exon selection across networks of functionally connected genes. In this opinion piece, we highlight recent publications that identify some of the molecular mechanisms-RNA and DNA binding proteins and epigenetic modifications-which direct cell-specific exon selection during pre-mRNA splicing. Aberrant splicing patterns are signature features of a growing number of diseases of the nervous system. Recent publications demonstrate the value of delineating basic mechanisms that dictate exon choice to inform the development of new therapeutic strategies that correct or compensate for damaging deficits in alternative splicing.
在神经元的生命周期中，剪接的动态变化支持了发育和可塑性，并且与疾病病理有关。细胞特异性剪接程序协调功能连接基因网络中的外显子选择。在这篇观点文章中，我们强调了最近的一些出版物，这些出版物确定了一些分子机制——RNA 和 DNA 结合蛋白和表观遗传修饰——在 pre-mRNA 剪接过程中指导细胞特异性外显子选择。异常剪接模式是越来越多神经系统疾病的特征。最近的出版物证明了描述决定外显子选择的基本机制的价值，这些机制为开发新的治疗策略提供了信息，这些策略可以纠正或补偿剪接中有害的缺陷。
