title: G-quadruplexes: Emerging roles in neurodegenerative diseases and the non-coding transcriptome.
abstract: G-rich sequences in DNA and RNA have a propensity to fold into stable secondary structures termed G-quadruplexes. G-quadruplex forming sequences are widespread throughout the human genome, within both, protein coding and non-coding genes, and regulatory regions. G-quadruplexes have been implicated in multiple cellular functions including chromatin epigenetic regulation, DNA recombination, transcriptional regulation of gene promoters and enhancers, and translation. Here we will review the evidence for the occurrence of G-quadruplexes both in vitro and in vivo; their role in neurological diseases including G-quadruplex-forming repeat expansions in the C9orf72 gene in frontotemporal dementia and amyotrophic lateral sclerosis and loss of the G-quadruplex binding protein FMRP in the intellectual disability fragile X syndrome. We also review mounting evidence that supports a role for G-quadruplexes in regulating the processing or function of a range of non-coding RNAs. Finally we will highlight current perspectives for therapeutic interventions that target G-quadruplexes.
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. Electronic address: r.simone@ucl.ac.uk.
authors.forename: Roberto
authors.initials: R
authors.lastname: Simone
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Sobell Department of Motor Neuroscience and Movement, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Gary N
authors.initials: GN
authors.lastname: Parkinson
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. Electronic address: a.isaacs@ucl.ac.uk.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Isaacs
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics*; D059467:Transcriptome
keywords: G-quadruplex; Neurodegenerative diseases; Non-coding RNA