Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
Biochem J. 2010 May 13;428(2):281-91. doi: 10.1042/BJ20100024.
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 BDNF 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-signal-regulated kinase 1/2) pathway, via both MSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms.
神经营养因子是在神经元发育和存活以及突触形成和可塑性中起重要作用的生长因子。神经营养因子的许多作用是通过改变转录或翻译导致蛋白质表达的变化来介导的。为了确定神经营养因子是否调节 microRNAs（miRNAs）的产生，miRNAs 是调节蛋白质翻译或 mRNA 稳定性的小 RNA 种类，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 miRNAs。这表明 miR-212/132 簇包含对 BDNF 处理反应最敏感的 miRNAs。该簇被发现产生四种 miRNAs：miR-132、miR-132*、miR-212 和 miR-212*。使用特定的抑制剂、小鼠模型和启动子分析，我们已经表明，miR-212/132 miRNA 簇及其衍生的 miRNAs 的转录调节受 ERK1/2（细胞外信号调节激酶 1/2）途径调控，通过 MSK（有丝分裂原和应激激活激酶）依赖和非依赖机制。
