RT Journal Article
T1 The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
A1 López de Silanes, Isabel
A1 Gorospe, Myriam
A1 Taniguchi, Hiroaki
A1 Abdelmohsen, Kotb
A1 Srikantan, Subramanya
A1 Alaminos, Miguel
A1 Berdasco, María
A1 Urdinguio, Rocío G
A1 Fraga, Mario F
A1 Jacinto, Filipe V
A1 Esteller, Manel
K1 Antígenos de Superficie
K1 Antineoplastic Agents
K1 Secuencia de Bases
K1 Línea Celular Tumoral
K1 Cisplatino
K1 ADN (Citosina-5-) Metiltransferasa
K1 Metilación de ADN
K1 Hu
K1 Datos de Secuencia Molecular
K1 Estabilidad del ARN
K1 RNA, Messenger
AB 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.
PB Oxford University Press
SN 0305-1048
YR 2009
FD 2009-05
LK http://hdl.handle.net/10668/697
UL http://hdl.handle.net/10668/697
LA en
NO 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
NO Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 11, 2025