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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: Ott, Claus-Eric (Author) , Grünhagen, Johannes (Author) , Jäger, Marten (Author) , Horbelt, Daniel (Author) , Schwill, Simon (Author) , Kallenbach, Klaus (Author) , Guo, Gao (Author) , Manke, Thomas (Author) , Knaus, Petra (Author) , Mundlos, Stefan (Author) , Robinson, Peter N. (Author)
Format: Article (Journal)
Language:English
Published: January 31, 2011
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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Summary: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.
Item Description:Gesehen am 19.10.2022
Physical Description:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0016250

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