Khudayberdiev Sharof, Fiore Roberto, Schratt Gerhard
Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, Universität Heidelberg; and Institut für Neuroanatomie, Universitätsklinikum Heidelberg, Heidelberg 69120, Germany.
Commun Integr Biol. 2009 Sep;2(5):411-3. doi: 10.4161/cib.2.5.8834.
Neuronal activity controls the correct establishment and refinement of neuronal circuits by regulating key aspects such as dendritogenesis and spine development. Both transcriptional and post-transcriptional gene expression programs induced by neuronal activity have to be coordinated in a tight spatio-temporal manner in order for proper functioning of the neuron. In this context microRNAs (miRNAs), which are implicated in post-transcriptional gene regulation, are good candidates to control dendritic and spine development. In a recent study we have demonstrated that neuronal activity induces myocyte enhancing factor 2 (Mef2) dependent transcription of a large cluster of brain-specific miRNAs (miR379-410). Expression of at least three microRNAs (miR-329,-134 and -381) from this cluster is essential for activity-dependent dendritic outgrowth of hippocampal neurons. One of these three miRNAs, miR-134, promotes dendritic outgrowth by inhibiting translation of the mRNA encoding the translational regulator Pumilio2 (Pum2). In brief, our results suggest a novel role for Mef2 in promoting activity-dependent dendritogenesis by inducing the transcription of the miR379-410 cluster.
神经元活动通过调节诸如树突发生和棘突发育等关键方面来控制神经元回路的正确建立和完善。为了使神经元正常运作,由神经元活动诱导的转录和转录后基因表达程序必须在紧密的时空方式上进行协调。在这种情况下,参与转录后基因调控的微小RNA(miRNA)是控制树突和棘突发育的良好候选者。在最近的一项研究中,我们已经证明神经元活动诱导了一大群脑特异性miRNA(miR379 - 410)的肌细胞增强因子2(Mef2)依赖性转录。该簇中至少三种微小RNA(miR - 329、- 134和- 381)的表达对于海马神经元的活性依赖性树突生长至关重要。这三种miRNA之一,miR - 134,通过抑制编码翻译调节因子Pumilio2(Pum2)的mRNA的翻译来促进树突生长。简而言之,我们的结果表明Mef2在通过诱导miR379 - 410簇的转录促进活性依赖性树突发生中具有新作用。