Léveillé, NicolasElkon, RanDavalos, VeronicaManoharan, VijayalaxmiHollingworth, DaveVrielink, Joachim OudeLe Sage, CarlosMelo, Carlos A.Horlings, Hugo M.Wesseling, JelleUle, JernejEsteller, ManelRamos, AndresAgami, Reuven2018-09-032018-09-032011-10-25https://hdl.handle.net/2445/124207MicroRNAs (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.11 p.application/pdfengcc by-nc-nd (c) Léveillé et al., 2011http://creativecommons.org/licenses/by-nc-nd/3.0/es/RNACàncer de mamaRNABreast cancerinfo:eu-repo/semantics/article2018-07-24info:eu-repo/semantics/openAccess22027593