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.; Guo, G.; Manke, T.; Knaus, P.; Mundlos, S.; Robinson, P. N.

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

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Manke, T.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Mundlos, S.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Robinson, P. N.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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引用

Ott, C. E., Grunhagen, J., Jager, M., Horbelt, D., Schwill, S., Kallenbach, K., Guo, G., Manke, T., Knaus, P., Mundlos, S., & Robinson, P. N. (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.

引用: https://hdl.handle.net/11858/00-001M-0000-0010-7832-D

要旨

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.