Journal
NUCLEIC ACIDS RESEARCH
Volume 39, Issue 16, Pages 7308-7315Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkr368
Keywords
-
Categories
Funding
- Ministry of Science and Higher Education (Poland) [N-N301-0171634]
- EU [POIG.01.03.01-30-098/08]
- European Community through the 'Integrated Infrastructure Initiative' [R II 3-CT-2004-506008]
- Foundation for Polish Science
Ask authors/readers for more resources
The CGG repeats are present in the 5'-untranslated region (5'-UTR) of the fragile X mental retardation gene FMR1 and are associated with two diseases: fragile X-associated tremor ataxia syndrome (FXTAS) and fragile X syndrome (FXS). FXTAS occurs when the number of repeats is 55-200 and FXS develops when the number exceeds 200. FXTAS is an RNA-mediated disease in which the expanded CGG tracts form stable structures and sequester important RNA binding proteins. We obtained and analysed three crystal structures of double-helical CGG repeats involving unmodified and 8-Br modified guanosine residues. Despite the presence of the non-canonical base pairs, the helices retain an A-form. In the G-G pairs one guanosine is always in the syn conformation, the other is anti. There are two hydrogen bonds between the Watson-Crick edge of G(anti) and the Hoogsteen edge of G(syn): O6 circle dot N1H and N7 circle dot N2H. The G(syn)-G(anti) pair shows affinity for binding ions in the major groove. G(syn) causes local unwinding of the helix, compensated elsewhere along the duplex. CGG helical structures appear relatively stable compared with CAG and CUG tracts. This could be an important factor in the RNA's ligand binding affinity and specificity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available