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C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes

Fratta, P; Mizielinska, S; Nicoll, AJ; Zloh, M; Fisher, EM; Parkinson, G; Isaacs, AM; (2012) C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Scientific Reports , 2 , Article 1016. 10.1038/srep01016. Green open access

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Other (JPG Figure 1: Schematic representation of the parallel stranded GGGGCC RNA G-quadruplex.)
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Other (JPG Figure 2: The C9orf72 hexanucleotide repeat is predicted to form a G-quadruplex structure.)
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Other (JPG Figure 3: NMR analysis of the C9orf72 GGGGCC RNA hexanucleotide repeat shows formation of G-quadruplexes.)
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Other (JPG Figure 4: CD analysis shows the GGGGCC RNA G-quadruplex structures are very stable, cation dependent and parallel oriented.)
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Abstract

Large expansions of a non-coding GGGGCC-repeat in the first intron of the C9orf72 gene are a common cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). G-rich sequences have a propensity for forming highly stable quadruplex structures in both RNA and DNA termed G-quadruplexes. G-quadruplexes have been shown to be involved in a range of processes including telomere stability and RNA transcription, splicing, translation and transport. Here we show using NMR and CD spectroscopy that the C9orf72 hexanucleotide expansion can form a stable G-quadruplex, which has profound implications for disease mechanism in ALS and FTD.

Type: Article
Title: C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/srep01016
Publisher version: http://dx.doi.org/10.1038/srep01016
Language: English
Additional information: PMCID: PMC3527825 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License [http://creativecommons.org/licenses/by-nc-nd/3.0/], You are free to share (copy, distribute and transmit the work), but you must attribute the author, you may not use this work for commercial purposes and you may not alter, transform, or build upon this work and distribute any derivative works you create under a similar license.
Keywords: Amyotrophic Lateral Sclerosis, DNA, DNA Repeat Expansion, Frontotemporal Dementia, G-Quadruplexes, Genotype, Humans, Nuclear Magnetic Resonance, Biomolecular, Proteins
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Neurodegenerative Diseases
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: http://discovery.ucl.ac.uk/id/eprint/1381390
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