title: C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes.
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.
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.forename: Sarah
authors.initials: S
authors.lastname: Mizielinska
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nicoll
authors.forename: Mire
authors.initials: M
authors.lastname: Zloh
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.forename: Gary
authors.initials: G
authors.lastname: Parkinson
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Isaacs
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D000073885:C9orf72 Protein; D004247:DNA / Q000235:genetics; D042622:DNA Repeat Expansion; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000378:metabolism; D054856:G-Quadruplexes; D005838:Genotype; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011506:Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; D004247:DNA