Tsang John, Zhu Jun, van Oudenaarden Alexander
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2007 Jun 8;26(5):753-67. doi: 10.1016/j.molcel.2007.05.018.
MicroRNAs (miRNAs) are regulatory molecules that participate in diverse biological processes in animals and plants. While thousands of mammalian genes are potentially targeted by miRNAs, the functions of miRNAs in the context of gene networks are not well understood. Specifically, it is unknown whether miRNA-containing networks have recurrent circuit motifs, as has been observed in regulatory networks of bacteria and yeast. Here we develop a computational method that utilizes gene expression data to show that two classes of circuits-corresponding to positive and negative transcriptional coregulation of a miRNA and its targets-are prevalent in the human and mouse genomes. Additionally, we find that neuronal-enriched miRNAs tend to be coexpressed with their target genes, suggesting that these miRNAs could be involved in neuronal homeostasis. Our results strongly suggest that coordinated transcriptional and miRNA-mediated regulation is a recurrent motif to enhance the robustness of gene regulation in mammalian genomes.
微小RNA（miRNA）是参与动植物多种生物过程的调控分子。虽然数千个哺乳动物基因可能是miRNA的靶标，但miRNA在基因网络背景下的功能尚未得到充分了解。具体而言，含miRNA的网络是否具有反复出现的回路基序尚不清楚，而细菌和酵母的调控网络中已观察到这种基序。在这里，我们开发了一种计算方法，利用基因表达数据表明，两类回路——对应于miRNA及其靶标的正向和负向转录共调控——在人类和小鼠基因组中普遍存在。此外，我们发现富含神经元的miRNA往往与其靶基因共表达，这表明这些miRNA可能参与神经元稳态。我们的结果强烈表明，协调的转录和miRNA介导的调控是增强哺乳动物基因组基因调控稳健性的反复出现的基序。
