title: Multiple microRNAs may regulate the DNA repair enzyme uracil-DNA glycosylase.
abstract: 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.
authors.forename: Siv A
authors.initials: SA
authors.lastname: Hegre
authors.forename: Pål
authors.initials: P
authors.lastname: Sætrom
authors.forename: Per A
authors.initials: PA
authors.lastname: Aas
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Pettersen
authors.forename: Marit
authors.initials: M
authors.lastname: Otterlei
authors.forename: Hans E
authors.initials: HE
authors.lastname: Krokan
mesh_terms: D020413:3' Untranslated Regions; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D051981:Uracil-DNA Glycosidase