Repression of translation of human estrogen receptor alpha by G-quadruplex formation.
Biochemistry
; 48(48): 11487-95, 2009 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-19860473
ABSTRACT
Tissue-specific expression of the human estrogen receptor alpha gene (ESR1) is achieved through multiple promoter sequences resulting in various mRNA transcripts encoding a common protein but differing in their 5'-untranslated region (5'-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulated through the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate that the human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonic regions. In particular, we show using CD, UV, and NMR spectroscopy that a stable DNA G-quadruplex motif is formed within the exon C gene sequence. This motif, which PCR shows is transcribed in normal and neoplastic endometrium and in MCF-7 cells, forms a stable RNA quadruplex demonstrable by CD and UV analysis. Cloning the exon C G-quadruplex sequence upstream of a luciferase reporter gene caused a 6-fold reduction of enzymatic activity compared to a mutant sequence. We conclude that the exon C G-quadruplex motif is present in the 5'-UTR of the mRNA transcript, where it modulates the efficiency of translation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
/
Receptor alfa de Estrogênio
/
Quadruplex G
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido