MicroRNAs (miRNAs) are small noncoding RNAs that act as negative regulators of gene expression in the cytoplasm. Yet, emerging evidence has shown that miRNAs are also distributed in the nucleus, with its function largely undetermined. At the same time, while miRNAs and enhancers show obvious tissue specificity, the interaction between miRNAs and enhancers in gene regulation remains unknown. By screening miRNA databases, we have identified a subset of miRNAs, called nuclear activating miRNAs (NamiRNAs). As enhancer regulators, NamiRNAs are able to activate gene expression at the transcriptional level. In addition, we found that the regulation of enhancers mediated by NamiRNAs depends on the presence of intact enhancers and AGO2 protein. More interesting is that NamiRNAs promote global gene transcription through the binding and activation of their targeted enhancers. Our results demonstrate a novel role for miRNA as an enhancer trigger for transcriptional gene activation. Further study of the function and molecular mechanism for NamiRNAs in tumorigenesis and development is of great significance.
Keywords: AGO2; Activation; Enhancer; NamiRNA; Tissue specificity; microRNA.