Journal article

Publication year: 2024

Pages: 8515-8533

Journal: Nucleic Acids Research

Volume number: 52

Issue number: 14

ISSN: 0305-1048

eISSN: 1362-4962

Open access status: Gold

DOI Link: https://doi.org/10.1093/nar/gkae416

Publisher: Oxford University Press

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.

Graphical Abstract

Harvard Citation style: Verheyden, N., Klostermann, M., Brueggemann, M., Steede, H., Scholz, A., Amr, S., et al. (2024) 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, Nucleic Acids Research, 52(14), pp. 8515-8533. https://doi.org/10.1093/nar/gkae416

APA Citation style: Verheyden, N., Klostermann, M., Brueggemann, M., Steede, H., Scholz, A., Amr, S., Lichtenthaeler, C., Muench, C., Schmid, T., Zarnack, K., & Krueger, A. (2024). 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. Nucleic Acids Research. 52(14), 8515-8533. https://doi.org/10.1093/nar/gkae416