Unknown

Dataset Information

0

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


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.

SUBMITTER: Leveille N 

PROVIDER: S-EPMC3221330 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 sho  ...[more]

Similar Datasets

| S-EPMC125723 | biostudies-literature
| S-EPMC5622327 | biostudies-literature
| S-EPMC8015715 | biostudies-literature
2019-09-23 | GSE113338 | GEO
| S-EPMC6377842 | biostudies-literature
| PRJNA450846 | ENA
| S-EPMC6340497 | biostudies-literature
| S-EPMC3245910 | biostudies-literature
| S-EPMC7093416 | biostudies-literature
| S-EPMC2664006 | biostudies-literature