Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity.
Nat Commun
; 2: 513, 2011 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-22027593
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Proteínas de Ligação a RNA
/
MicroRNAs
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Holanda