title: RNA-dominant diseases.
abstract: Several examples have come to light in which mutations in non-protein-coding regions give rise to a deleterious gain-of-function by non-coding RNA. Expression of the toxic RNA is associated with formation of nuclear inclusions and late-onset degenerative changes in brain, heart or skeletal muscle. In the best studied example, myotonic dystrophy, it appears that the main pathogenic effect of the toxic RNA is to sequester binding proteins and compromise the regulation of alternative splicing. This review describes some of the recent advances in understanding the pathophysiology of RNA-dominant diseases.
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Osborne
authors.forename: Charles A
authors.initials: CA
authors.lastname: Thornton
mesh_terms: D017398:Alternative Splicing; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D000071058:Huntingtin Protein; D008957:Models, Genetic; D009223:Myotonic Dystrophy / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D022661:RNA, Untranslated / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; C493663:MBNL1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins