MicroRNAs Activate Gene Transcription Epigenetically as an Enhancer Trigger

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that function as enhancer regulator. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger.

微小RNA（MicroRNAs, miRNAs）是一类小型非编码RNA，作为基因表达负调控因子发挥功能。越来越多的研究证据表明，除了在细胞质中发挥作用外，miRNAs亦可定位于细胞核内。然而，细胞核内miRNAs的功能意义在很大程度上仍未得到充分阐明。通过对miRNA数据库进行筛选，我们鉴定出了一类兼具增强子调控功能的miRNA亚群。本研究中，我们发现一系列miRNA具备基因激活功能。我们以miR-24-1为研究对象，发现该miRNA通过靶向增强子以非常规方式激活基因转录。与之一致的是，当利用转录激活因子样效应物核酸酶（Transcription Activator-Like Effector Nucleases, TALEN）敲除该增强子序列后，该激活效应完全消失。进一步研究表明，miR-24-1可上调增强子RNA（enhancer RNA, eRNA）的表达、改变组蛋白修饰状态，并增强p300与RNA聚合酶II（RNA Polymerase II, RNA Pol II）在该增强子位点的富集。本研究结果揭示了miRNA作为增强子触发因子的全新作用机制。