Multiple microRNAs may regulate the DNA repair enzyme uracil-DNA glycosylase

► MicroRNAs miR-16, miR-34c, and miR-199a down-regulate uracil-DNA glycosylase. ► The microRNAs target conserved seed sites in the 3′UTR. ► Down-regulation was demonstrated both at the mRNA and the protein level. Human nuclear uracil-DNA glycosylase UNG2 is essential for post-replicative repair of uracil in DNA, and UNG2 protein and mRNA levels rapidly decline in G2/M phase. Previous work has demonstrated regulation of UNG2 at the transcriptional level, as well as by protein phosphorylation and ubiquitylation. UNG2 mRNA, encoded by the UNG gene, contains a long 3′untranslated region (3′UTR) of previously unknown function. Here, we demonstrate that several conserved regions in the 3′UTR are potential seed sites for microRNAs (miRNAs), such as miR-16, miR-34c, and miR-199a. Our results show that these miRNAs down-regulate UNG activity, UNG mRNA, and UNG protein levels. Down-regulation was dependent on the 3′UTR, indicating that the miRNAs directly target the conserved seed sites in the 3′UTR. These results add miRNAs as a new modality to UNG's increasing list of complex regulatory mechanisms.