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Heart Structure-Specific Transcriptomic Atlas Reveals Conserved microRNA-mRNA Interactions

posted on 02.01.2013, 01:27 by Caterina Vacchi-Suzzi, Florian Hahne, Philippe Scheubel, Magali Marcellin, Valerie Dubost, Magdalena Westphal, Catherine Boeglen, Stine Büchmann-Møller, Ming Sin Cheung, André Cordier, Christopher De Benedetto, Mark Deurinck, Moritz Frei, Pierre Moulin, Edward Oakeley, Olivier Grenet, Armelle Grevot, Robert Stull, Diethilde Theil, Jonathan G. Moggs, Estelle Marrer, Philippe Couttet

MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development and cardiovascular diseases. 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-enriched (miR-1) and valve-enriched (miR-125b-5p and miR-204) microRNAs was confirmed using in situ hybridization. MicroRNA-mRNA interactions potentially relevant for cardiac functions were explored using anti-correlation expression analysis and microRNA target prediction algorithms. Interactions between miR-1/Timp3, miR-125b/Rbm24, miR-204/Tgfbr2 and miR-208b/Csnk2a2 were identified and experimentally investigated 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 that provides a novel resource for investigating novel microRNA regulatory circuits involved in cardiac molecular physiopathology.