Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins
Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins
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DOI：
10.1042/bj20100024
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发表时间：
2010-06-01
影响因子：
4.1
通讯作者：
Arthur, J. Simon C.
中科院分区：
文献类型：
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作者：
Remenyi, Judit;Hunter, Christopher J.;Arthur, J. Simon C.
神经营养素是对神经元发育和存活以及突触形成和可塑性非常重要的生长因子。神经营养素的许多作用是由转录或翻译改变导致的蛋白质表达变化介导的。为了确定神经营养因子是否调节 microRNA (miRNA)（调节蛋白质翻译或 mRNA 稳定性的小 RNA 种类）的产生，我们使用深度测序来鉴定培养的原代皮质小鼠神经元中 BDNF（脑源性神经营养因子）诱导的 miRNA。这表明 miR-212/132 簇包含对 BDNE 治疗最敏感的 miRNA。该簇被发现产生四种 miRNA：miR-132、miR-132*、miR-212 和 miR-212*。通过使用特定的抑制剂、小鼠模型和启动子分析，我们发现 miR-212/132 miRNA 簇及其衍生的 miRNA 的转录调节受到 ERK1/2（细胞外信号调节激酶 1/2）途径的调节，通过 MSK（丝裂原和应激激活激酶）依赖性和非依赖性机制。
Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in protein expression as a result of altered transcription or translation. To determine whether neurotrophins regulate the production of microRNAs (miRNAs), small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify BDNF (brain-derived neurotrophic factor)-induced miRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the miRNAs most responsive to BDNE treatment. This cluster was found to produce four miRNAs: miR-132, miR-132*, miR-212 and miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 miRNA cluster and the miRNAs derived from it are regulated by the ERK1/2 (extracellular-signalregulated kinase 1/2) pathway, via both MSK (mitogen and stressactivated kinase)-dependent and -independent mechanisms.