MicroRNAs Differentially Expressed in Postnatal Aortic Development Downregulate Elastin via 3′ UTR and Coding-Sequence Binding Sites

被引：92

作者：

Ott, Claus Eric ^{[1
]}

Gruenhagen, Johannes ^{[1
]}

Jaeger, Marten ^{[1
,2
]}

Horbelt, Daniel ^{[3
]}

Schwill, Simon ^{[4
]}

Kallenbach, Klaus ^{[4
]}

Guo, Gao ^{[1
]}

Manke, Thomas ^{[5
]}

Knaus, Petra ^{[3
]}

Mundlos, Stefan ^{[1
,2
,5
]}

Robinson, Peter N. ^{[1
,2
,5
]}

机构：

[1] Charite, Inst Med Genet, D-13353 Berlin, Germany

[2] Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, D-13353 Berlin, Germany

[3] Free Univ Berlin, Inst Biochem, D-1000 Berlin, Germany

[4] Univ Heidelberg Hosp, Dept Cardiac Surg, Heidelberg, Germany

[5] Max Planck Inst Mol Genet, Berlin, Germany

来源：

PLOS ONE | 2011年 / 6卷 / 01期

关键词：

GROWTH-FACTOR-BETA; MESSENGER-RNA; FIBER FORMATION; MARKED LONGEVITY; D-ASPARTATE; TGF-BETA; PROTEIN; TRANSCRIPTION; TARGETS; COLLAGEN;

D O I：

10.1371/journal.pone.0016250

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 68 条

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