title: MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3' UTR and coding-sequence binding sites.
abstract: Elastin production is characteristically turned off during the maturation of elastin-rich organs such as the aorta. MicroRNAs (miRNAs) are small regulatory RNAs that down-regulate target mRNAs by binding to miRNA regulatory elements (MREs) typically located in the 3' UTR. Here we show a striking up-regulation of miR-29 and miR-15 family miRNAs during murine aortic development with commensurate down-regulation of targets including elastin and other extracellular matrix (ECM) genes. There were a total of 14 MREs for miR-29 in the coding sequences (CDS) and 3' UTR of elastin, which was highly significant, and up to 22 miR-29 MREs were found in the CDS of multiple ECM genes including several collagens. This overrepresentation was conserved throughout mammalian evolution. Luciferase reporter assays showed synergistic effects of miR-29 and miR-15 family miRNAs on 3' UTR and coding-sequence elastin constructs. Our results demonstrate that multiple miR-29 and miR-15 family MREs are characteristic for some ECM genes and suggest that miR-29 and miR-15 family miRNAs are involved in the down-regulation of elastin in the adult aorta.
authors.affiliation: Institute for Medical Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claus Eric
authors.initials: CE
authors.lastname: Ott
authors.forename: Johannes
authors.initials: J
authors.lastname: Grünhagen
authors.forename: Marten
authors.initials: M
authors.lastname: Jäger
authors.forename: Daniel
authors.initials: D
authors.lastname: Horbelt
authors.forename: Simon
authors.initials: S
authors.lastname: Schwill
authors.forename: Klaus
authors.initials: K
authors.lastname: Kallenbach
authors.forename: Gao
authors.initials: G
authors.lastname: Guo
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.forename: Petra
authors.initials: P
authors.lastname: Knaus
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001011:Aorta / Q000254:growth & development*; D001665:Binding Sites; D015536:Down-Regulation / Q000235:genetics*; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016366:Open Reading Frames; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C544301:Mirn15a microRNA, mouse; D004549:Elastin