MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3′ UTR and coding-sequence binding sites

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-...

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Hauptverfasser: Ott, Claus-Eric (VerfasserIn) , Grünhagen, Johannes (VerfasserIn) , Jäger, Marten (VerfasserIn) , Horbelt, Daniel (VerfasserIn) , Schwill, Simon (VerfasserIn) , Kallenbach, Klaus (VerfasserIn) , Guo, Gao (VerfasserIn) , Manke, Thomas (VerfasserIn) , Knaus, Petra (VerfasserIn) , Mundlos, Stefan (VerfasserIn) , Robinson, Peter N. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: January 31, 2011
In: PLOS ONE
Year: 2011, Jahrgang: 6, Heft: 1, Pages: 1-12
ISSN:1932-6203
DOI:10.1371/journal.pone.0016250
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0016250
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0016250
Volltext
Verfasserangaben:Claus Eric Ott, Johannes Grünhagen, Marten Jäger, Daniel Horbelt, Simon Schwill, Klaus Kallenbach, Gao Guo, Thomas Manke, Petra Knaus, Stefan Mundlos, Peter N. Robinson
Beschreibung
Zusammenfassung: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.
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Beschreibung:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0016250