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Research Paper
Secondary Structure and Dynamics of the r(CGG) Repeat in the mRNA of the Fragile X Mental Retardation 1 (FMR1) Gene
Marta Zumwalt, Anna Ludwig, Paul J. Hagerman and Thorsten Dieckmann
volume 4 | issue 2
april/may/june 2007Pages: 93 - 100
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The CGG triplet repeat found within the 5’UTR of the FMR1 gene is involved in the pathogenesis of both fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). The repeat has been shown to form both hairpins and tetraplexes in DNA; however, the secondary structure of CGG-repeat RNA has not been well defined. To this end, we have performed NMR spectroscopy on in vitro transcribed CGG-repeat RNAs and see clear evidence of intramolecular hairpins, with no evidence of tetraplex structures. Both C•G and G◦G base pairs form in the hairpin stem, though in a dynamic equilibrium of conformations. In addition, we investigated the effect of an AGG repeat interruption on hairpin stability; such interruptions are often interspersed within the CGG repeat element and are thought to modulate secondary structure of the RNA. While the AGG repeat lowers the Tm of the hairpin at low Mg2+ concentrations, this difference disappears at physiological Mg2+ levels.
Authors
Marta Zumwalt
Department of Chemistry, University of California at Davis, Davis, California USA
Anna Ludwig
Department of Biochemistry and Molecular Medicine, University of California at Davis, Davis, California USA
Paul J. Hagerman
Department of Biochemistry and Molecular Medicine, University of California at Davis, Davis, California USA
Thorsten Dieckmann
Department of Chemistry, University of Waterloo, Waterloo, ON, Canada