title: Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions.
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 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.
authors.affiliation: Preclinical Safety, Novartis Institutes of Biomedical Research, Basel, Switzerland.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vacchi-Suzzi
authors.forename: Florian
authors.initials: F
authors.lastname: Hahne
authors.forename: Philippe
authors.initials: P
authors.lastname: Scheubel
authors.forename: Magali
authors.initials: M
authors.lastname: Marcellin
authors.forename: Valerie
authors.initials: V
authors.lastname: Dubost
authors.forename: Magdalena
authors.initials: M
authors.lastname: Westphal
authors.forename: Catherine
authors.initials: C
authors.lastname: Boeglen
authors.forename: Stine
authors.initials: S
authors.lastname: Büchmann-Møller
authors.forename: Ming Sin
authors.initials: MS
authors.lastname: Cheung
authors.forename: André
authors.initials: A
authors.lastname: Cordier
authors.forename: Christopher
authors.initials: C
authors.lastname: De Benedetto
authors.forename: Mark
authors.initials: M
authors.lastname: Deurinck
authors.forename: Moritz
authors.initials: M
authors.lastname: Frei
authors.forename: Pierre
authors.initials: P
authors.lastname: Moulin
authors.forename: Edward
authors.initials: E
authors.lastname: Oakeley
authors.forename: Olivier
authors.initials: O
authors.lastname: Grenet
authors.forename: Armelle
authors.initials: A
authors.lastname: Grevot
authors.forename: Robert
authors.initials: R
authors.lastname: Stull
authors.forename: Diethilde
authors.initials: D
authors.lastname: Theil
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Moggs
authors.forename: Estelle
authors.initials: E
authors.lastname: Marrer
authors.forename: Philippe
authors.initials: P
authors.lastname: Couttet
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping / Q000379:methods; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006351:Heart Valves / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger