A comparative analysis of heart microRNAs in vertebrates brings novel insights into the evolution of genetic regulatory networks

dc.contributor.authorNachtigall, Pedro G. [UNESP]
dc.contributor.authorBovolenta, Luiz A. [UNESP]
dc.contributor.authorPatton, James G.
dc.contributor.authorFromm, Bastian
dc.contributor.authorLemke, Ney [UNESP]
dc.contributor.authorPinhal, Danillo [UNESP]
dc.contributor.institutionInstituto Butantan
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionVanderbilt University
dc.contributor.institutionStockholm University
dc.date.accessioned2021-06-25T10:55:23Z
dc.date.available2021-06-25T10:55:23Z
dc.date.issued2021-12-01
dc.description.abstractBackground: During vertebrate evolution, the heart has undergone remarkable changes that lead to morphophysiological differences in the fully formed heart of these species, such as chamber septation, heart rate frequency, blood pressure, and cardiac output volume. Despite these differences, the heart developmental process is guided by a core gene set conserved across vertebrates. Nonetheless, the regulatory mechanisms controlling the expression of genes involved in heart development and maintenance are largely uncharted. MicroRNAs (miRNAs) have been described as important regulatory elements in several biological processes, including heart biology. These small RNA molecules are broadly conserved in sequence and genomic context in metazoans. Mutations may occur in miRNAs and/or genes that contribute to the establishment of distinct repertoires of miRNA-target interactions, thereby favoring the differential control of gene expression and, consequently, the origin of novel phenotypes. In fact, several studies showed that miRNAs are integrated into genetic regulatory networks (GRNs) governing specific developmental programs and diseases. However, studies integrating miRNAs in vertebrate heart GRNs under an evolutionary perspective are still scarce. Results: We comprehensively examined and compared the heart miRNome of 20 species representatives of the five major vertebrate groups. We found 54 miRNA families with conserved expression and a variable number of miRNA families with group-specific expression in fishes, amphibians, reptiles, birds, and mammals. We also detected that conserved miRNAs present higher expression levels and a higher number of targets, whereas the group-specific miRNAs present lower expression levels and few targets. Conclusions: Both the conserved and group-specific miRNAs can be considered modulators orchestrating the core and peripheral genes of heart GRNs of vertebrates, which can be related to the morphophysiological differences and similarities existing in the heart of distinct vertebrate groups. We propose a hypothesis to explain evolutionary differences in the putative functional roles of miRNAs in the heart GRNs analyzed. Furthermore, we present new insights into the molecular mechanisms that could be helping modulate the diversity of morphophysiology in the heart organ of vertebrate species.en
dc.description.affiliationLaboratório Especial de Toxinologia Aplicada (LETA) CeTICS Instituto Butantan
dc.description.affiliationDepartment of Chemical and Biological Sciences Institute of Biosciences of Botucatu São Paulo State University (UNESP)
dc.description.affiliationDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University (UNESP)
dc.description.affiliationDepartment of Biological Sciences Vanderbilt University
dc.description.affiliationDepartment of Molecular Biosciences The Wenner-Gren Institute (MBW) Stockholm University
dc.description.affiliationUnespDepartment of Chemical and Biological Sciences Institute of Biosciences of Botucatu São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University (UNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2012/15589-7
dc.description.sponsorshipIdFAPESP: 2013/06864-7
dc.identifierhttp://dx.doi.org/10.1186/s12864-021-07441-4
dc.identifier.citationBMC Genomics, v. 22, n. 1, 2021.
dc.identifier.doi10.1186/s12864-021-07441-4
dc.identifier.issn1471-2164
dc.identifier.scopus2-s2.0-85102542627
dc.identifier.urihttp://hdl.handle.net/11449/207454
dc.language.isoeng
dc.relation.ispartofBMC Genomics
dc.sourceScopus
dc.subjectCardiac miRNAs
dc.subjectComparative genomics
dc.subjectFunctional genomics
dc.subjectGenetic regulatory network
dc.subjectNon-coding RNA
dc.subjectSmall RNA
dc.titleA comparative analysis of heart microRNAs in vertebrates brings novel insights into the evolution of genetic regulatory networksen
dc.typeArtigo
unesp.author.orcid0000-0002-3196-0173[1]

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