The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA

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-t...

Descripción completa

Detalles Bibliográficos
Autores: 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, 1968-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126639
Acceso en línea:https://hdl.handle.net/2445/126639
Access Level:acceso abierto
Palabra clave:RNA
ADN
DNA
id ES_c3a3a1433cde05c99a88bc953bc4e8e2
oai_identifier_str oai:diposit.ub.edu:2445/126639
network_acronym_str ES
network_name_str España
repository_id_str
spelling The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNALópez de Silanes, IsabelGorospe, MyriamTaniguchi, HiroakiAbdelmohsen, KotbSrikantan, SubramanyaAlaminos, MiguelBerdasco, MaríaUrdinguio, Rocío G.Fraga, Mario F.Jacinto, Filipe V.Esteller, Manel, 1968-RNAADNDNAThe 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 3UTR 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 RTqPCR 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.Oxford University Press2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/126639Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1093/nar/gkp123Nucleic Acids Research, 2009, vol. 37, num. 8, p. 2658-2671https://doi.org/10.1093/nar/gkp123info:eu-repo/grantAgreement/EC/FP7/200620cc by-nc (c) López de Silanes et al., 2009http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1266392026-05-27T06:46:51Z
dc.title.none.fl_str_mv The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
title The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
spellingShingle The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
López de Silanes, Isabel
RNA
ADN
DNA
title_short The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
title_full The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
title_fullStr The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
title_full_unstemmed The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
title_sort The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
dc.creator.none.fl_str_mv 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, 1968-
author López de Silanes, Isabel
author_facet 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, 1968-
author_role author
author2 Gorospe, Myriam
Taniguchi, Hiroaki
Abdelmohsen, Kotb
Srikantan, Subramanya
Alaminos, Miguel
Berdasco, María
Urdinguio, Rocío G.
Fraga, Mario F.
Jacinto, Filipe V.
Esteller, Manel, 1968-
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RNA
ADN
DNA
topic RNA
ADN
DNA
description 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 3UTR 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 RTqPCR 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.
publishDate 2009
dc.date.none.fl_str_mv 2009
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126639
url https://hdl.handle.net/2445/126639
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/nar/gkp123
Nucleic Acids Research, 2009, vol. 37, num. 8, p. 2658-2671
https://doi.org/10.1093/nar/gkp123
info:eu-repo/grantAgreement/EC/FP7/200620
dc.rights.none.fl_str_mv cc by-nc (c) López de Silanes et al., 2009
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) López de Silanes et al., 2009
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418813017030656
score 15,300719

Similares en LA Referencia