Occurrence of a quadruplex motif in a unique insert within exon C of the bovine estrogen receptor α gene (ESR1)

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

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The 5′ end of exon C of the bovine estrogen receptor α gene (bov-ESR1) includes a unique G-rich insert, not found in other closely related mammalian genes, which lies close to both a double E-box transcription factor binding site and the site of a single nucleotide (G/A) polymorphism. Biophysical studies, using CD and UV absorbance measurements, show that this 22 base insert leads to the formation of a family of stable G-quadruplex structures which are unaffected by the G/A polymorphism. Multiplex PCR shows that the region including the G-quadruplex is transcribed into RNA, and studies with a synthetic RNA transcript sequence demonstrated formation of a highly stable parallel-folded quadruplex structure. Luciferase reporter constructs demonstrate that the G-rich sequence reduces rates of translation when present in the 5′-UTR of mRNA transcripts. Mutations (GGG to AAA) that destabilize the quadruplex lead to a 15-fold enhancement of translational efficiency, suggesting that a possible biological role of the insert in exon C of the bov-ESR1 is to regulate translation of this exon.

Original languageEnglish (US)
Pages (from-to)7625-7633
Number of pages9
JournalBiochemistry
Volume49
Issue number35
DOIs
StatePublished - Sep 7 2010

ASJC Scopus subject areas

  • Biochemistry

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    Derecka, K., Balkwill, G. D., Garner, T. P., Hodgman, C., Flint, A. P. F., & Searle, M. S. (2010). Occurrence of a quadruplex motif in a unique insert within exon C of the bovine estrogen receptor α gene (ESR1). Biochemistry, 49(35), 7625-7633. https://doi.org/10.1021/bi100804f