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Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions

Vacchi-Suzzi, Caterina and Hahne, Florian and Scheubel, Philippe and Marcellin, Magali and Dubost, Valerie and Kalteis, Magdalena and Boeglen, Catherine and Buechmann-Moller, Stine and Cheung, Nicole and Cordier, Andre and De Benedetto, Christopher and Deurinck, Mark and Frei, Moritz and Moulin, Pierre and Oakeley, Edward James and Grenet, Olivier and Grevot, Armelle and Stull, Robert and Theil, Diethilde and Moggs, Jonathan and Marrer, Estelle and Couttet, Philippe (2013) Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions. PLoS ONE, 8 (1). e52442. ISSN 1932-6203

Abstract

MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development and cardiovascular disease. Here, we have characterized the expression and distribution of microRNAs across eight cardiac structures (left and right ventricles, apex, papillary muscle, septum, left and right atrium and valves) in rat, Beagle dog and Cynomolgus monkey using microRNA sequencing. Conserved microRNA signatures enriched in specific heart structures across these species were identified for cardiac valve (miR-let-7c, miR-125b, miR-127, miR-199a-3p, miR-204, miR-320, miR-99b, miR-328 and miR-744) and myocardium (miR-1, miR-133b, miR-133a, miR-208b, miR-30e, miR-499-5p, miR-30e*). The relative abundance of myocardium- (miR-1) and valve-enriched (miR-125b-5p and miR-204) microRNAs was confirmed using in situ hybridization. Potential microRNA-mRNA interactions were explored using anti-correlation expression analysis in matched samples and microRNA target prediction algorithms. These included miR-1/Timp3, miR-125b/Rbm24, miR-204/Tgfbr2 and miR-208b/Csnk2a2, for which miR-mediated post-transcriptional inhibition was confirmed by over-expression in human pulmonary smooth muscle cells and luciferase reporter assays. In conclusion, we have generated a high-resolution heart structure-specific mRNA/microRNA expression atlas for three mammalian species relevant to biomedical research and uncovered novel microRNA regulatory circuits that provide a novel resource for investigating cardiac molecular physiopathology.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/7879

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