Repression of translation of human estrogen receptor α by G-quadruplex formation

Graham D. Balkwill, Kamila Derecka, Thomas P. Garner, Charlie Hodgman, A. P F Flint, Mark S. Searle

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Tissue-specific expression of the human estrogen receptor α 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 DNAG-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.

Original languageEnglish (US)
Pages (from-to)11487-11495
Number of pages9
JournalBiochemistry
Volume48
Issue number48
DOIs
StatePublished - Dec 8 2009
Externally publishedYes

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G-Quadruplexes
Estrogen Receptors
Exons
Genes
5' Untranslated Regions
Developmental Genes
Messenger RNA
MCF-7 Cells
Endometrium
Luciferases
Reporter Genes
Organism Cloning
Estrogens
Transcription Factors
Magnetic Resonance Spectroscopy
RNA
Cloning
Polymerase Chain Reaction
Ultraviolet spectroscopy
Nuclear magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Balkwill, G. D., Derecka, K., Garner, T. P., Hodgman, C., Flint, A. P. F., & Searle, M. S. (2009). Repression of translation of human estrogen receptor α by G-quadruplex formation. Biochemistry, 48(48), 11487-11495. https://doi.org/10.1021/bi901420k

Repression of translation of human estrogen receptor α by G-quadruplex formation. / Balkwill, Graham D.; Derecka, Kamila; Garner, Thomas P.; Hodgman, Charlie; Flint, A. P F; Searle, Mark S.

In: Biochemistry, Vol. 48, No. 48, 08.12.2009, p. 11487-11495.

Research output: Contribution to journalArticle

Balkwill, GD, Derecka, K, Garner, TP, Hodgman, C, Flint, APF & Searle, MS 2009, 'Repression of translation of human estrogen receptor α by G-quadruplex formation', Biochemistry, vol. 48, no. 48, pp. 11487-11495. https://doi.org/10.1021/bi901420k
Balkwill GD, Derecka K, Garner TP, Hodgman C, Flint APF, Searle MS. Repression of translation of human estrogen receptor α by G-quadruplex formation. Biochemistry. 2009 Dec 8;48(48):11487-11495. https://doi.org/10.1021/bi901420k
Balkwill, Graham D. ; Derecka, Kamila ; Garner, Thomas P. ; Hodgman, Charlie ; Flint, A. P F ; Searle, Mark S. / Repression of translation of human estrogen receptor α by G-quadruplex formation. In: Biochemistry. 2009 ; Vol. 48, No. 48. pp. 11487-11495.
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