INTEC Inc., 1-3-3 Shinsuna, Koto-ku, Tokyo 136-8637, Japan.
BMC Genomics. 2013;14 Suppl 2(Suppl 2):S3. doi: 10.1186/1471-2164-14-S2-S3. Epub 2013 Feb 15.
microRNAs (miRNAs) are tiny endogenous RNAs that have been discovered in animals and plants, and direct the post-transcriptional regulation of target mRNAs for degradation or translational repression via binding to the 3'UTRs and the coding exons. To gain insight into the biological role of miRNAs, it is essential to identify the full repertoire of mRNA targets (target genes). A number of computer programs have been developed for miRNA-target prediction. These programs essentially focus on potential binding sites in 3'UTRs, which are recognized by miRNAs according to specific base-pairing rules.
Here, we introduce a novel method for miRNA-target prediction that is entirely independent of existing approaches. The method is based on the hypothesis that transcription of a miRNA and its target genes tend to be co-regulated by common transcription factors. This hypothesis predicts the frequent occurrence of common cis-elements between promoters of a miRNA and its target genes. That is, our proposed method first identifies putative cis-elements in a promoter of a given miRNA, and then identifies genes that contain common putative cis-elements in their promoters. In this paper, we show that a significant number of common cis-elements occur in ~28% of experimentally supported human miRNA-target data. Moreover, we show that the prediction of human miRNA-targets based on our method is statistically significant. Further, we discuss the random incidence of common cis-elements, their consensus sequences, and the advantages and disadvantages of our method.
This is the first report indicating prevalence of transcriptional regulation of a miRNA and its target genes by common transcription factors and the predictive ability of miRNA-targets based on this property.
微小 RNA（miRNAs）是在动物和植物中发现的微小内源性 RNA，通过与 3'UTR 和编码外显子结合，指导靶 mRNA 的转录后调控，导致靶 mRNA 的降解或翻译抑制。为了深入了解 miRNAs 的生物学功能，识别 mRNA 靶标（靶基因）的全部组成是至关重要的。已经开发了许多用于 miRNA 靶预测的计算机程序。这些程序本质上侧重于 3'UTR 中的潜在结合位点，miRNAs 根据特定的碱基配对规则识别这些结合位点。
在这里，我们介绍了一种全新的 miRNA 靶预测方法，该方法完全独立于现有方法。该方法基于以下假设：miRNA 和其靶基因的转录往往受到共同转录因子的共同调控。该假设预测 miRNA 和其靶基因的启动子之间常见顺式元件的频繁出现。也就是说，我们提出的方法首先识别给定 miRNA 启动子中的假定顺式元件，然后识别其启动子中含有共同假定顺式元件的基因。在本文中，我们表明，在~28%的实验支持的人类 miRNA 靶数据中存在大量常见顺式元件。此外，我们表明，基于我们的方法预测人类 miRNA 靶标在统计学上是显著的。此外，我们还讨论了常见顺式元件的随机发生、它们的共识序列以及我们方法的优缺点。
这是第一个表明 miRNA 和其靶基因的转录受共同转录因子调控以及基于该特性预测 miRNA 靶标的普遍性的报告。
