title: R-loops highlight the nucleus in ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative disease linked to mutations in various genes implicated in cytoplasmic RNA metabolism. Recent studies from genetic models have also helped reveal connections between various ALS-linked factors and RNA-DNA hybrid (R-loop) regulation. Here, we examine how such hybrid-regulatory processes are pointing to a key role for the nucleus in ALS. We also present a potential molecular mechanism in which hybrids may represent at least one of the long sought after missing links between different ALS genes. Our opinion is that RNA-DNA hybrids will play a key role in deciphering ALS and other human diseases.
authors.affiliation: a Department of Laboratory Medicine and Pathobiology; Faculty of Medicine ; University of Toronto ; Toronto , ON Canada.
authors.forename: Jayesh S
authors.initials: JS
authors.lastname: Salvi
authors.forename: Karim
authors.initials: K
authors.lastname: Mekhail
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D004247:DNA / Q000235:genetics*; D025461:Feedback, Physiological; D006801:Humans; D012313:RNA / Q000235:genetics*
chemical_list: D012313:RNA; D004247:DNA
keywords: Amyotrophic lateral sclerosis (ALS); Ataxin2; C9ORF72; FUS; R-loop; RNA-DNA hybrid; SOD1; Senataxin; TDP43; genome instability; stress granules