Journal
NATURE COMMUNICATIONS
Volume 2, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms1519
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Funding
- ERC (European Research Council)
- KWF (koningin wilhelmina fonds
- Dutch cancer foundation)
- Horizon-NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek)
- EMBO long-term fellowship
- Medical Research Council [U117574558]
- Medical Research Council [MC_U105185858, MC_U117533887, MC_U117574558] Funding Source: researchfish
- MRC [MC_U117533887, MC_U117574558, MC_U105185858] Funding Source: UKRI
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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.
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