title: RNA Structures as Mediators of Neurological Diseases and as Drug Targets.
abstract: RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this Review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate the study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Viachaslau
authors.initials: V
authors.lastname: Bernat
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address: disney@scripps.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Disney
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D057180:Frontotemporal Dementia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009223:Myotonic Dystrophy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D059370:RNA Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D024801:Tauopathies / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D012313:RNA