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.
Author:Nikita A. VerheydenORCiD, Melina KlostermannORCiD, Mirko BrüggemannORCiDGND, Anica ScholzGND, Shady AmrORCiD, Chiara Lichtenthäler, Christian MünchORCiD, Tobias SchmidORCiDGND, Katharina ZarnackORCiDGND, Andreas KruegerORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2023/09/12
Date of first Publication:2023/09/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/09/13
Page Number:35
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International