Argonaute-dependent ribosome-associated protein quality control

Gao, Yajie; Zhu, Yuanxiang; Sun, Qing; Chen, Dahua

doi:10.1016/j.tcb.2022.07.007

Cited by 8 publications

(2 citation statements)

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“…Our study biochemically validates this unusual group of miR-181 targets in primary cells and uncovers that this pool of targets is selectively regulated by translational inhibition on top of RNA destabilization. This suggests that translational inhibition in this case may be a feature of miRNA-mediated gene regulation, when binding of multiple RISCs induces ribosome stalling on mRNA, rather than competition of RISC components with initiation factors for cap binding [3][4][5] . Notably, base-pairing analysis revealed no common composition of this subgroup of MREs, as has been proposed by others 5 .…”

Section: Discussionmentioning

confidence: 99%

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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

Verheyden,

Klostermann,

Brüggemann

et al. 2023

Preprint

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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.HighlightsDeep 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 destabilizationin 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.

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Section: Discussionmentioning

confidence: 99%

“…Commonly, miRNA-loaded RISCs recruit exonucleases to rapidly degrade the targeted mRNA. Alternatively, RISC-associated factors may compete with translation initiation factors for cap binding or cause ribosome stalling, both resulting in translational inhibition [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%