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

  • 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.

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Metadaten
Author:Nikita A. VerheydenORCiD, Melina KlostermannORCiDGND, Mirko BrüggemannORCiDGND, Hanna M. Steede, Anica ScholzGND, Shady AmrORCiD, Chiara Lichtenthäler, Christian MünchORCiDGND, Tobias SchmidORCiDGND, Katharina ZarnackORCiDGND, Andreas KruegerORCiDGND
URN:urn:nbn:de:hebis:30:3-835864
URL:http://10.1101/2023.09.08.556730v2
DOI:https://doi.org/10.1101/2023.09.08.556730
Parent Title (English):bioRxiv
Publisher:bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2024/03/26
Date of first Publication:2024/03/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/04/14
Issue:2023.09.08.556730 Version 2
Edition:Version 2
Page Number:37
HeBIS-PPN:517909448
Institutes:Medizin
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International