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Outside the limit: questioning the distance restrictions for cooperative miRNA binding sites.
Diener, Caroline; Hart, Martin; Fecher-Trost, Claudia; Knittel, Jessica; Rheinheimer, Stefanie; Meyer, Markus R; Mayer, Jens; Flockerzi, Veit; Keller, Andreas; Meese, Eckart.
Afiliação
  • Diener C; Institute of Human Genetics, Saarland University, 66421, Homburg, Germany. caroline.diener@uni-saarland.de.
  • Hart M; Institute of Human Genetics, Saarland University, 66421, Homburg, Germany.
  • Fecher-Trost C; Department of Experimental and Clinical Pharmacology & Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
  • Knittel J; Institute of Human Genetics, Saarland University, 66421, Homburg, Germany.
  • Rheinheimer S; Institute of Human Genetics, Saarland University, 66421, Homburg, Germany.
  • Meyer MR; Department of Experimental and Clinical Toxicology & Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
  • Mayer J; Institute of Human Genetics, Saarland University, 66421, Homburg, Germany.
  • Flockerzi V; Department of Experimental and Clinical Pharmacology & Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
  • Keller A; Chair for Clinical Bioinformatics, Saarland Informatics Campus, Saarland University, 66123, Saarbrücken, Germany.
  • Meese E; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), 66123, Saarbrücken, Germany.
Cell Mol Biol Lett ; 28(1): 8, 2023 Jan 24.
Article em En | MEDLINE | ID: mdl-36694129
Among the concepts in biology that are widely taken granted is a potentiated cooperative effect of multiple miRNAs on the same target. This strong hypothesis contrasts insufficient experimental evidence. The quantity as well as the quality of required side constraints of cooperative binding remain largely hidden. For miR-21-5p and miR-155-5p, two commonly investigated regulators across diseases, we selected 15 joint target genes. These were chosen to represent various neighboring 3'UTR binding site constellations, partially exceeding the distance rules that have been established for over a decade. We identified different cooperative scenarios with the binding of one miRNA enhancing the binding effects of the other miRNA and vice versa. Using both, reporter assays and whole proteome analyses, we observed these cooperative miRNA effects for genes that bear 3'UTR binding sites at distances greater than the previously defined limits. Astonishingly, the experiments provide even stronger evidence for cooperative miRNA effects than originally postulated. In the light of these findings the definition of targetomes specified for single miRNAs need to be refined by a concept that acknowledges the cooperative effects of miRNAs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Mol Biol Lett Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Mol Biol Lett Ano de publicação: 2023 Tipo de documento: Article