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Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity

Léveillé, N; Elkon, R; Davalos, V; Manoharan, V; Hollingworth, D; Oude Vrielink, J; le Sage, C; ... Agami, R; + view all (2011) Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity. Nature Communications , 2 , Article 513. 10.1038/ncomms1519. Green open access

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Abstract

MicroRNAs (miRNAs) interact with 3'-untranslated regions of messenger RNAs to restrict expression of most protein-coding genes during normal development and cancer. RNA-binding proteins (RBPs) can control the biogenesis, stability and activity of miRNAs. Here we identify RBM38 in a genetic screen for RBPs whose expression controls miRNA access to target mRNAs. RBM38 is induced by p53 and its ability to modulate miRNA-mediated repression is required for proper p53 function. In contrast, RBM38 shows lower propensity to block the action of the p53-controlled miR-34a on SIRT1. Target selectivity is determined by the interaction of RBM38 with uridine-rich regions near miRNA target sequences. Furthermore, in large cohorts of human breast cancer, reduced RBM38 expression by promoter hypermethylation correlates with wild-type p53 status. Thus, our results indicate a novel layer of p53 gene regulation, which is required for its tumour suppressive function.

Type: Article
Title: Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms1519
Publisher version: http://dx.doi.org/10.1038/ncomms1519
Language: English
Additional information: This work is licensed under a Creative Commons Attribution-NonCommercial- NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/3.0/ PMCID: PMC3221330
Keywords: 3' Untranslated Regions, Cell Cycle, Cell Line, Tumor, DNA Methylation, Flow Cytometry, Humans, Magnetic Resonance Spectroscopy, MicroRNAs, Microscopy, Fluorescence, Promoter Regions, Genetic, RNA-Binding Proteins, Real-Time Polymerase Chain Reaction, Tumor Suppressor Protein p53
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1392074
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