Verheyden, Nikita ANikita AVerheydenKlostermann, MelinaMelinaKlostermannBrüggemann, MirkoMirkoBrüggemannSteede, Hanna MHanna MSteedeScholz, AnicaAnicaScholzAmr, ShadyShadyAmrLichtenthaeler, ChiaraChiaraLichtenthaelerMünch, ChristianChristianMünchSchmid, TobiasTobiasSchmidZarnack, KathiKathiZarnackKrueger, AndreasAndreasKrueger2024-11-012024-11-012024https://jlupub.ub.uni-giessen.de/handle/jlupub/19748https://doi.org/10.22029/jlupub-19105MicroRNAs (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.enNamensnennung 4.0 Internationalddc:570