TY - JOUR
T1 - Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity
AU - Léveillé, Nicolas
AU - Elkon, Ran
AU - Davalos, Veronica
AU - Manoharan, Vijayalaxmi
AU - Hollingworth, Dave
AU - Oude Vrielink, Joachim
AU - le Sage, Carlos
AU - Melo, Carlos A.
AU - Horlings, Hugo M.
AU - Wesseling, Jelle
AU - Ule, Jernej
AU - Esteller, Manel
AU - Ramos, Andres
AU - Agami, Reuven
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - https://doi.org/10.1038/ncomms1519
DO - https://doi.org/10.1038/ncomms1519
M3 - Article
C2 - 22027593
SN - 2041-1723
VL - 2
SP - 513
JO - Nature communications
JF - Nature communications
ER -