Understanding the Modus Operandi of MicroRNA Regulatory Clusters

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dc.contributor.authorOliveira, Arthur C. [UNESP]
dc.contributor.authorBovolenta, Luiz A. [UNESP]
dc.contributor.authorAlves, Lucas [UNESP]
dc.contributor.authorFigueiredo, Lucas [UNESP]
dc.contributor.authorRibeiro, Amanda O. [UNESP]
dc.contributor.authorCampos, Vinicius F.
dc.contributor.authorLemke, Ney [UNESP]
dc.contributor.authorPinhal, Danillo [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionFederal University of Pelotas
dc.date.accessioned2020-12-12T02:09:43Z
dc.date.available2020-12-12T02:09:43Z
dc.date.issued2019-09-18
dc.description.abstractMicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest.en
dc.description.affiliationInstitute of Biosciences of Botucatu Department of Genetics Sao Paulo State University (UNESP)
dc.description.affiliationDepartment of Physics and Biophysics Sao Paulo State University (UNESP)
dc.description.affiliationLaboratory of Structural Genomics (GenEstrut) Technology Developmental Center Graduate Program of Biotechnology Federal University of Pelotas
dc.description.affiliationUnespInstitute of Biosciences of Botucatu Department of Genetics Sao Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Physics and Biophysics Sao Paulo State University (UNESP)
dc.identifierhttp://dx.doi.org/10.3390/cells8091103
dc.identifier.citationCells, v. 8, n. 9, 2019.
dc.identifier.doi10.3390/cells8091103
dc.identifier.issn2073-4409
dc.identifier.lattes7977035910952141
dc.identifier.scopus2-s2.0-85085905259
dc.identifier.urihttp://hdl.handle.net/11449/200555
dc.language.isoeng
dc.relation.ispartofCells
dc.sourceScopus
dc.subjectfunctional enrichment
dc.subjectgene regulatory networks
dc.subjectmicroRNA modules
dc.subjectmicroRNA regulation
dc.subjectmRNA fold-change
dc.titleUnderstanding the Modus Operandi of MicroRNA Regulatory Clustersen
dc.typeArtigo
unesp.author.lattes7977035910952141
unesp.author.orcid0000-0003-0063-0179[1]
unesp.author.orcid0000-0002-8116-8280[2]
unesp.author.orcid0000-0003-4730-8670[3]
unesp.author.orcid0000-0002-1241-8039[4]
unesp.author.orcid0000-0002-1396-391X[5]
unesp.author.orcid0000-0003-2119-293X[6]
unesp.author.orcid0000-0001-7463-4303[7]
unesp.author.orcid0000-0003-1075-0182[8]

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