神经元形态发生,集成到电路中,突触连接的重塑发生在时间和空间定义的步骤中。因此,蛋白质的表达和有助于这些过程的特定蛋白质同工型必须在时间和空间上进行定量控制。各种各样的转录后调控机制,作用于pre-mRNA和mRNA分子有助于这种控制。因此,它们严重参与生理和病理生理神经系统的发育,函数,和维护。这里,我们回顾了mRNA代谢如何促进神经元发育的最新发现,从神经干细胞维持到突触规范,特别关注轴突的生长,指导,分支,和突触形成。我们强调RNA结合蛋白的作用,并强调了它们在对RNA编辑的分子过程知之甚少中的新兴作用,选择性聚腺苷酸化,和拼接的时间控制,在讨论替代拼接的同时,RNA定位,本地翻译。我们用进化保守的武藏蛋白家族的例子来说明单个RNA结合蛋白是如何的,一方面,作用于不同的RNA代谢过程,and,另一方面,影响神经元发育和电路形成的多个步骤。最后,我们提供了与RNA结合蛋白功能异常和转录后调控中断相关的疾病的联系.
Neuronal morphogenesis, integration into circuits, and remodeling of synaptic connections occur in temporally and spatially defined steps. Accordingly, the expression of proteins and specific protein isoforms that contribute to these processes must be controlled quantitatively in time and space. A wide variety of post-transcriptional regulatory mechanisms, which act on pre-mRNA and mRNA molecules contribute to this control. They are thereby critically involved in physiological and pathophysiological nervous system development, function, and maintenance. Here, we review recent findings on how mRNA metabolism contributes to neuronal development, from neural stem cell maintenance to synapse specification, with a particular focus on axon growth, guidance, branching, and synapse formation. We emphasize the role of RNA-binding proteins, and highlight their emerging roles in the poorly understood molecular processes of RNA editing, alternative polyadenylation, and temporal control of splicing, while also discussing alternative splicing, RNA localization, and local translation. We illustrate with the example of the evolutionary conserved Musashi protein family how individual RNA-binding proteins are, on the one hand, acting in different processes of RNA metabolism, and, on the other hand, impacting multiple steps in neuronal development and circuit formation. Finally, we provide links to diseases that have been associated with the malfunction of RNA-binding proteins and disrupted post-transcriptional regulation.