Targeting and Regulation of Epstein-Barr Virus Origin of DNA Replication by MicroRNA Hsa-miR-155. Homo sapiens

MicroRNAs (miRNAs) are a class of small RNA molecules previously known to function as post-transcriptional regulators in multiple cellular processes. Here, we show that a human cellular miRNA, hsa-miR-155, can regulate the latent replication origin (oriP) of Epstein-Barr virus (EBV) by competing with Epstein-Barr nuclear antigen 1 (EBNA-1) for direct binding to the dyad symmetry (DS) sequence on the oriP, and thus regulate the function of the DNA replication origin. When this direct binding was abolished by introducing a mutation into the hsa-miR-155 or DS sequence, replication resumed. Furthermore, endogenous hsa-miR-155 could target specifically to the EBV genomic replication origin in EBV type I-latently infected cells and regulate the viral DNA replication. Our discovery represents a hitherto undiscovered and important function of miRNA for the control of DNA replication, and demonstrates a probable mechanism of how this can be achieved using the latent replication origin of EBV. Overall design: In this sequencing, miR-155, miR-3117 and miR-control (based on miR-67) were used to evaluate the targeting sequence in DS element of EBV.