Occurrence of a quadruplex motif in a unique insert within exon C of the bovine estrogen receptor alpha gene (ESR1).
The 5' end of exon C of the bovine estrogen receptor alpha 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.
Derecka
Kamila
K
School of Biosciences, Division of Animal Sciences, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK.
Balkwill
Graham D
GD
Garner
Thomas P
TP
Hodgman
Charlie
C
Flint
Anthony P F
AP
Searle
Mark S
MS
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002942:Circular Dichroism; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005091:Exons; D054856:G-Quadruplexes; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000235:genetics
D020121:5' Untranslated Regions; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger