A G-quadruplex structure within the 5'-UTR of TRF2 mRNA represses translation in human cells.
Nucleic Acids Res
; 38(20): 7187-98, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20571083
ABSTRACT
Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G-quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5'-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5'-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2GRNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5'-UTR TRF2RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
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Regiões 5' não Traduzidas
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Proteína 2 de Ligação a Repetições Teloméricas
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Sequências Reguladoras de Ácido Ribonucleico
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Quadruplex G
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM