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G‐quadruplexes: Emerging roles in neurodegenerative diseases and the non‐coding transcriptome
Author(s) -
Simone Roberto,
Fratta Pietro,
Neidle Stephen,
Parkinson Gary N.,
Isaacs Adrian M.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.05.003
Subject(s) - biology , epigenetics , enhancer , genetics , gene , chromatin , trinucleotide repeat expansion , transcriptome , computational biology , non coding rna , c9orf72 , frontotemporal dementia , rna , gene expression , dementia , disease , medicine , allele , pathology
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.