Rajman Marek, Schratt Gerhard
Biochemisch-Pharmakologisches Centrum, Institut für Physiologische Chemie, Philipps-Universität Marburg, Marburg 35043, Germany.
Biochemisch-Pharmakologisches Centrum, Institut für Physiologische Chemie, Philipps-Universität Marburg, Marburg 35043, Germany
Development. 2017 Jul 1;144(13):2310-2322. doi: 10.1242/dev.144337.
The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. It is well-established that transcriptional programs play major roles in neural circuit development. However, in recent years, post-transcriptional control of gene expression has emerged as an additional, and probably equally important, regulatory layer. In particular, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation. It is also becoming clear that miRNAs are frequently dysregulated in neurodevelopmental disorders, suggesting a role for miRNAs in the etiology and/or maintenance of neurological disease states. Here, we provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as 'master regulators' or 'fine-tuners' of gene expression, depending on context, to influence processes such as cell fate determination, cell migration, neuronal polarization and synapse formation.
认知和行为需要神经网络的正常形成和功能。事实上，破坏神经网络的病理生理状态可导致神经发育障碍，如自闭症、精神分裂症或智力残疾。转录程序在神经回路发育中起主要作用，这一点已得到充分证实。然而，近年来，基因表达的转录后调控已成为另一个可能同样重要的调控层面。特别是，已表明微小RNA（miRNA），一类丰富的小调控RNA，可通过控制例如局部mRNA翻译来调节神经回路的发育、成熟和功能。越来越清楚的是，miRNA在神经发育障碍中经常失调，这表明miRNA在神经系统疾病状态的病因和/或维持中起作用。在这里，我们概述了控制神经发育的最突出的调控性miRNA，强调它们如何根据具体情况作为基因表达的“主调控因子”或“微调器”，影响细胞命运决定、细胞迁移、神经元极化和突触形成等过程。
