title: "Seed-Milarity" confers to hsa-miR-210 and hsa-miR-147b similar functional activity.
abstract: Specificity of interaction between a microRNA (miRNA) and its targets crucially depends on the seed region located in its 5'-end. It is often implicitly considered that two miRNAs sharing the same biological activity should display similarity beyond the strict six nucleotide region that forms the seed, in order to form specific complexes with the same mRNA targets. We have found that expression of hsa-miR-147b and hsa-miR-210, though triggered by different stimuli (i.e. lipopolysaccharides and hypoxia, respectively), induce very similar cellular effects in term of proliferation, migration and apoptosis. Hsa-miR-147b only shares a "minimal" 6-nucleotides seed sequence with hsa-miR-210, but is identical with hsa-miR-147a over 20 nucleotides, except for one base located in the seed region. Phenotypic changes induced after heterologous expression of miR-147a strikingly differ from those induced by miR-147b or miR-210. In particular, miR-147a behaves as a potent inhibitor of cell proliferation and migration. These data fit well with the gene expression profiles observed for miR-147b and miR-210, which are very similar, and the gene expression profile of miR-147a, which is distinct from the two others. Bioinformatics analysis of all human miRNA sequences indicates multiple cases of miRNAs from distinct families exhibiting the same kind of similarity that would need to be further characterized in terms of putative functional redundancy. Besides, it implies that functional impact of some miRNAs can be masked by robust expression of miRNAs belonging to distinct families.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire-IPMC, Centre National de la Recherche Scientifique, CNRS UMR 7275, Sophia Antipolis, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertero
authors.forename: Sébastien
authors.initials: S
authors.lastname: Grosso
authors.forename: Karine
authors.initials: K
authors.lastname: Robbe-Sermesant
authors.forename: Kevin
authors.initials: K
authors.lastname: Lebrigand
authors.forename: Imene-Sarah
authors.initials: IS
authors.lastname: Hénaoui
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Puisségur
authors.forename: Sandra
authors.initials: S
authors.lastname: Fourre
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Mazure
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponzio
authors.forename: Bruno
authors.initials: B
authors.lastname: Cardinaud
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Roger
authors.initials: R
authors.lastname: Rezzonico
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: C572377:MIRN147 microRNA, human; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger