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

2012; Nature Portfolio; Volume: 2; Issue: 1 Linguagem: Inglês

10.1038/srep01016

2045-2322

Pietro Fratta, Sarah Mizielinska, Andrew J. Nicoll, Mire Zloh, Elizabeth Fisher, Gary N. Parkinson, Adrian M. Isaacs,

Amyotrophic Lateral Sclerosis Research

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.