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- W4386693655 abstract "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. Highlights Deep profiling identifies 6,729 miR-181 MREs in primary murine thymocytes. Novel miR-181 targets are associated with the control of global gene expression, including epigenetic and RNA regulation. miR-181 primarily acts through mRNA destabilization in vivo . 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." @default.
- W4386693655 created "2023-09-13" @default.
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- W4386693655 date "2023-09-12" @default.
- W4386693655 modified "2023-09-30" @default.
- W4386693655 title "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" @default.
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- W4386693655 doi "https://doi.org/10.1101/2023.09.08.556730" @default.
- W4386693655 hasPublicationYear "2023" @default.
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