Title:
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Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity
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Author:
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Léveillé, Nicolas; Elkon, Ran; Davalos, Veronica; Manoharan, Vijayalaxmi; Hollingworth, Dave; Vrielink, Joachim Oude; Le Sage, Carlos; Melo, Carlos A.; Horlings, Hugo M.; Wesseling, Jelle; Ule, Jernej; Esteller, Manel; Ramos, Andres; Agami, Reuven
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Abstract:
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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. |
Subject(s):
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-RNA -Càncer de mama -RNA -Breast cancer |
Rights:
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cc by-nc-nd (c) Léveillé et al., 2011
http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
Document type:
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Article Article - Published version |
Published by:
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Nature Publishing Group
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