A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis
A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis
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DOI：
10.1073/pnas.0508448102
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发表时间：
2005-11-08
影响因子：
11.1
通讯作者：
Impey, S
中科院分区：
文献类型：
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作者：
Vo, N;Klein, ME;Impey, S
microRNA（miRNAs）通过控制mRNA转录物的稳定性或翻译来调节细胞命运。尽管miRNA表达的空间和时间模式受到严格控制，但对诱导其表达的信号和转录调控机制知之甚少。此外，很少有miRNA靶点已被实验验证。通过全基因组筛选将miRNA miR132鉴定为转录因子cAMP反应元件结合蛋白（CREB）的靶点。miR132在神经元中富集，并且像许多神经元CREB靶标一样，被神经营养因子高度诱导。miR132在皮质神经元中的表达诱导神经突生长。相反，miR132功能的抑制减弱了神经元的生长。我们提供的证据表明，miR132通过降低GTP酶激活蛋白p250GAP的水平来调节神经元的形态发生。这些数据表明，CREB调节的miRNA调节神经元的形态发生通过响应外部营养线索。
MicroRNAs (miRNAs) regulate cellular fate by controlling the stability or translation of mRNA transcripts. Although the spatial and temporal patterning of miRNA expression is tightly controlled, little is known about signals that induce their expression nor mechanisms of their transcriptional regulation. Furthermore, few miRNA targets have been validated experimentally. The miRNA, miR132, was identified through a genome-wide screen as a target of the transcription factor, cAMP-response element binding protein (CREB). miR132 is enriched in neurons and, like many neuronal CREB targets, is highly induced by neurotrophins. Expression of miR132 in cortical neurons induced neurite outgrowth. Conversely, inhibition of miR132 function attenuated neuronal outgrowth. We provide evidence that miR132 regulates neuronal morphogenesis by decreasing levels of the GTPase-activating protein, p250GAP. These data reveal that a CREB-regulated miRNA regulates neuronal morphogenesis by responding to extrinsic trophic cues.