Manakov Sergei A, Grant Seth G N, Enright Anton J
European Bioinformatics Institute, Hinxton, Cambridge CB101SD, UK.
BMC Genomics. 2009 Sep 8;10:419. doi: 10.1186/1471-2164-10-419.
Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are now recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. While specific microRNAs are known to be involved in neural development, the extent to which global microRNA and mRNA profiles are coordinately regulated in neural development is unknown.
We examined mouse primary neuronal cultures, analyzing microRNA and mRNA expression. Three main developmental patterns of microRNA expression were observed: steady-state levels, up-regulated and down-regulated. Co-expressed microRNAs were found to have related target recognition sites and to be encoded in distinct genomic locations. A number of 43 differentially expressed miRNAs were located in five genomic clusters. Their predicted mRNA targets show reciprocal levels of expression. We identified a set of reciprocally expressed microRNAs that target mRNAs encoding postsynaptic density proteins and high-level steady-state microRNAs that target non-neuronal low-level expressed mRNAs.
We characterized hundreds of miRNAs in neuronal culture development and identified three major modes of miRNA expression. We predict these miRNAs to regulate reciprocally expressed protein coding genes, including many genes involved in synaptogenesis. The identification of miRNAs that target mRNAs during synaptogenesis indicates a new level of regulation of the synapse.
已知突触形成和神经网络的发育受mRNA合成的协调程序控制。现在人们认识到，微小RNA（microRNA）是多种生物体中mRNA翻译和稳定性的重要调节因子。虽然已知特定的微小RNA参与神经发育，但在神经发育过程中，全局微小RNA和mRNA谱的协调调节程度尚不清楚。
我们检查了小鼠原代神经元培养物，分析了微小RNA和mRNA的表达。观察到微小RNA表达的三种主要发育模式：稳态水平、上调和下调。发现共表达微小RNA具有相关的靶标识别位点，并在不同的基因组位置编码。43个差异表达的微小RNA位于五个基因组簇中。它们预测的mRNA靶标显示出相反的表达水平。我们鉴定出一组相互表达的微小RNA，其靶向编码突触后密度蛋白的mRNA，以及一组高水平稳态微小RNA，其靶向非神经元低水平表达mRNA。
我们在神经元培养发育中表征了数百种微小RNA，并鉴定出微小RNA表达的三种主要模式。我们预测这些微小RNA可调节相互表达的蛋白质编码基因，包括许多参与突触形成的基因。在突触形成过程中靶向mRNA的微小RNA的鉴定表明了突触调节的一个新水平。
