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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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 31, 2011
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| In: |
PLOS ONE
Year: 2011, Volume: 6, Issue: 1, Pages: 1-12 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0016250 |
| Online Access: | 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 
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| Author Notes: | Claus Eric Ott, Johannes Grünhagen, Marten Jäger, Daniel Horbelt, Simon Schwill, Klaus Kallenbach, Gao Guo, Thomas Manke, Petra Knaus, Stefan Mundlos, Peter N. Robinson |
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| 245 | 1 | 0 | |a MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3′ UTR and coding-sequence binding sites |c Claus Eric Ott, Johannes Grünhagen, Marten Jäger, Daniel Horbelt, Simon Schwill, Klaus Kallenbach, Gao Guo, Thomas Manke, Petra Knaus, Stefan Mundlos, Peter N. Robinson |
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| 520 | |a 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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