TY  - INPR
A1  - Verheyden, Nikita A.
A1  - Klostermann, Melina
A1  - Brüggemann, Mirko
A1  - Scholz, Anica
A1  - Amr, Shady
A1  - Lichtenthäler, Chiara
A1  - Münch, Christian
A1  - Schmid, Tobias
A1  - Zarnack, Katharina
A1  - Krueger, Andreas
T1  - 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
T2  - bioRxiv
N2  - 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.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75638
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-756386
UR  - https://www.biorxiv.org/content/10.1101/2023.09.08.556730v1
IS  - 2023.09.08.556730
ER  -