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Title: The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
Authors: López de Silanes, Isabel
Gorospe, Myriam
Taniguchi, Hiroaki
Abdelmohsen, Kotb
Srikantan, Subramanya
Alaminos, Miguel
Berdasco, María
Urdinguio, Rocío G
Fraga, Mario F
Jacinto, Filipe V
Esteller, Manel
metadata.dc.contributor.authoraffiliation: [Lopez de Silanes,I; Taniguchi,H; Berdasco,M; Urdinguio,RG; Fraga,MF; Jacinto,FV; Esteller M] Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Gorospe, M; Abdelmohsen K] Laboratory of Cellular and Molecular Biology, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, USA. [Alaminos,M ] Department of Histology, Granada University and Hospital Clinico Foundation, Granada. [Esteller,M] Institucio Catalana de Recerca i Estudis Avanc¸ ats (ICREA), Barcelona. [Esteller,M] Cancer Epigenetics and Biology Program (PEBC), Catalan Institute of Oncology (ICO), Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), L’Hospitalet, Barcelona, Catalonia, Spain.
Keywords: Antígenos de Superficie;Antineoplastic Agents;Secuencia de Bases;Línea Celular Tumoral;Cisplatino;ADN (Citosina-5-) Metiltransferasa;Metilación de ADN;Hu;Datos de Secuencia Molecular;Estabilidad del ARN;RNA, Messenger
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Chlorine Compounds::Cisplatin
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::One-Carbon Group Transferases::Methyltransferases::DNA Modification Methylases::DNA-Cytosine Methylases::DNA (Cytosine-5-)-Methyltransferase
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA Methylation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::RNA Stability
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nucleoproteins::RNA-Binding Proteins
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::One-Carbon Group Transferases::Methyltransferases::Protein Methyltransferases
Issue Date: May-2009
Publisher: Oxford University Press
Citation: López de Silanes I, Gorospe M, Taniguchi H, Abdelmohsen K, Srikantan S, Alaminos M, et al. The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA. Nucleic Acids Res.. 2009 May; 37(8):2658-71
Abstract: The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that the expression of DNMT3b is post-transcriptionally regulated by HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. The presence of a putative HuR-recognition motif in the DNMT3b 3'UTR prompted studies to investigate if this transcript associated with HuR. The interaction between HuR and DNMT3b mRNA was studied by immunoprecipitation of endogenous HuR ribonucleoprotein complexes followed by RT-qPCR detection of DNMT3b mRNA, and by in vitro pulldown of biotinylated DNMT3b RNAs followed by western blotting detection of HuR. These studies revealed that binding of HuR stabilized the DNMT3b mRNA and increased DNMT3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [HuR-DNMT3b mRNA] complex, in turn promoting DNMT3b mRNA decay, decreasing DNMT3b abundance, and lowering the methylation of repeated sequences and global DNA methylation. In summary, our data identify DNMT3b mRNA as a novel HuR target, present evidence that HuR affects DNMT3b expression levels post-transcriptionally, and reveal the functional consequences of the HuR-regulated DNMT3b upon DNA methylation patterns.
Description: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
metadata.dc.identifier.doi: 10.1093/nar/gkp123
ISSN: 0305-1048
Appears in Collections:SAS - Hospital Universitario San Cecilio

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