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

dc.contributor.authorVerheyden, Nikita A
dc.contributor.authorKlostermann, Melina
dc.contributor.authorBrüggemann, Mirko
dc.contributor.authorSteede, Hanna M
dc.contributor.authorScholz, Anica
dc.contributor.authorAmr, Shady
dc.contributor.authorLichtenthaeler, Chiara
dc.contributor.authorMünch, Christian
dc.contributor.authorSchmid, Tobias
dc.contributor.authorZarnack, Kathi
dc.contributor.authorKrueger, Andreas
dc.date.accessioned2024-11-01T14:20:43Z
dc.date.available2024-11-01T14:20:43Z
dc.date.issued2024
dc.description.abstractMicroRNAs (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.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG); ROR-ID:018mejw64
dc.identifier.urihttps://jlupub.ub.uni-giessen.de/handle/jlupub/19748
dc.identifier.urihttps://doi.org/10.22029/jlupub-19105
dc.language.isoen
dc.rightsNamensnennung 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddcddc:570
dc.titleA high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match
dc.typearticle
local.affiliationFB 08 - Biologie und Chemie
local.projectSFB 902-B15, KR 2320/7-1, GRK 2355/2, SFB 902-B13, FOR 2333-TP2
local.source.articlenumbergkae416
local.source.epage19
local.source.journaltitleNucleic acids research
local.source.spage1
local.source.urihttps://doi.org/10.1093/nar/gkae416
local.source.volume116

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