A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match
A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match
Abstract MicroRNAs (miRNAs) are critical post-transcriptional regulators in many biological processes. They act by guiding RNA-induced silencing complexes to miRNA response elements (MREs) in target mRNAs, inducing translational inhibition and/or mRNA degradation. Functional MREs are expected to predominantly occur in the 3’ untranslated region and involve perfect base-pairing of the miRNA seed. Here, we generate a high-resolution map of miR-181a/b-1 (miR-181) MREs to define the targeting rules of miR-181 in developing murine T-cells. By combining a multi-omics approach with computational high-resolution analyses, we uncover novel miR-181 targets and demonstrate that miR-181 acts predominantly through RNA destabilization. Importantly, we discover an alternative seed match and identify a distinct set of targets with repeat elements in the coding sequence which are targeted by miR-181 and mediate translational inhibition. In conclusion, deep profiling of MREs in primary cells is critical to expand physiologically relevant targetomes and establish context-dependent miRNA targeting rules. Key Points? Deep profiling identifies novel targets of miR-181 associated with global gene regulation.? miR-181 MREs in repeat elements in the coding sequence act through translational inhibition.? High-resolution analysis reveals an alternative seed match in functional MREs.
M¨1nch Christian、Lichtenthaeler Chiara、Amr Shady、Zarnack Kathi、Schmid Tobias、Steede Hanna M.、Scholz Anica、Verheyden Nikita A.、Klostermann Melina、Krueger Andreas、Br¨1ggemann Mirko
Institute of Biochemistry II, Faculty of Medicine, Goethe University FrankfurtInstitute of Molecular Medicine, Faculty of Medicine, Goethe University FrankfurtInstitute of Biochemistry II, Faculty of Medicine, Goethe University FrankfurtBuchmann Institute for Molecular Life Sciences & Institute of Molecular Biosciences, Goethe University FrankfurtInstitute of Biochemistry I, Faculty of Medicine, Goethe University FrankfurtMolecular Immunology, Justus Liebig University Gie?enInstitute of Biochemistry I, Faculty of Medicine, Goethe University FrankfurtMolecular Immunology, Justus Liebig University Gie?enBuchmann Institute for Molecular Life Sciences & Institute of Molecular Biosciences, Goethe University FrankfurtMolecular Immunology, Justus Liebig University Gie?enBuchmann Institute for Molecular Life Sciences & Institute of Molecular Biosciences, Goethe University Frankfurt
分子生物学遗传学细胞生物学
miRNA targetomemiR-181T-cell developmentthymuschimeric eCLIPribosome footprinting
M¨1nch Christian,Lichtenthaeler Chiara,Amr Shady,Zarnack Kathi,Schmid Tobias,Steede Hanna M.,Scholz Anica,Verheyden Nikita A.,Klostermann Melina,Krueger Andreas,Br¨1ggemann Mirko.A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2023.09.08.556730.点此复制
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