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

Ott, C. E., Grunhagen, J., Jager, M., Horbelt, D., Schwill, S., Kallenbach, K., et al. (2011). MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3' UTR and coding-sequence binding sites. PLoS ONE, 6(1), e16250. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21305018 http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0016250&representation=PDF.

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 Creators:
Ott, C. E., Author
Grunhagen, J., Author
Jager, M., Author
Horbelt, D., Author
Schwill, S., Author
Kallenbach, K., Author
Guo, G., Author
Manke, T.1, Author              
Knaus, P., Author
Mundlos, S.2, Author              
Robinson, P. N.2, Author              
Affiliations:
1Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: *3' Untranslated Regions; Animals; Aorta/*growth & development; Binding Sites; Down-Regulation/*genetics; Elastin/*biosynthesis/genetics; Extracellular Matrix/genetics; Gene Expression Regulation, Developmental; Mice; MicroRNAs/genetics/metabolism/*physiology; *Open Reading Frames; Regulatory Elements, Transcriptional/*genetics
 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.

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 Dates: 2011
 Publication Status: Published in print
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Title: PLoS ONE
Source Genre: Journal
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Pages: - Volume / Issue: 6 (1) Sequence Number: - Start / End Page: e16250 Identifier: ISSN: 1932-6203 (Electronic) 1932-6203 (Linking)