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

        Author
        Fratta, Pietro
        Mizielinska, Sarah
        Nicoll, Andrew J
        Zloh, Mire
        Fisher, Elizabeth M. C.
        Parkinson, Gary
        Isaacs, Adrian M.
        Attention
        2299/10424
        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.
        Publication date
        2012
        Published in
        Scientific Reports
        Published version
        https://doi.org/10.1038/srep01016
        Other links
        http://hdl.handle.net/2299/10424
        Relations
        School of Life and Medical Sciences
        Metadata
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