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

Nicolas Léveillé, Ran Elkon, Veronica Davalos, Vijayalaxmi Manoharan, Dave Hollingworth, Joachim Oude Vrielink, Carlos le Sage, Carlos A. Melo, Hugo M. Horlings, Jelle Wesseling, Jernej Ule, Manel Esteller, Andres Ramos and Reuven Agami ()
Additional contact information
Nicolas Léveillé: The Netherlands Cancer Institute, Plesmanlaan 121
Ran Elkon: The Netherlands Cancer Institute, Plesmanlaan 121
Veronica Davalos: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Av. Gran Via de L'Hospitalet 199-203, 08908 L'Hospitalet de Llobregat, Barcelona
Vijayalaxmi Manoharan: MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Dave Hollingworth: MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Joachim Oude Vrielink: The Netherlands Cancer Institute, Plesmanlaan 121
Carlos le Sage: The Netherlands Cancer Institute, Plesmanlaan 121
Carlos A. Melo: The Netherlands Cancer Institute, Plesmanlaan 121
Hugo M. Horlings: Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Jelle Wesseling: The Netherlands Cancer Institute
Jernej Ule: Medical Research Council Laboratory of Molecular Biology
Manel Esteller: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Av. Gran Via de L'Hospitalet 199-203, 08908 L'Hospitalet de Llobregat, Barcelona
Andres Ramos: MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Reuven Agami: The Netherlands Cancer Institute, Plesmanlaan 121

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: 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.

Date: 2011
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1519 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1519

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1519

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().