title: RNA mis-splicing in disease.
abstract: The human transcriptome is composed of a vast RNA population that undergoes further diversification by splicing. Detecting specific splice sites in this large sequence pool is the responsibility of the major and minor spliceosomes in collaboration with numerous splicing factors. This complexity makes splicing susceptible to sequence polymorphisms and deleterious mutations. Indeed, RNA mis-splicing underlies a growing number of human diseases with substantial societal consequences. Here, we provide an overview of RNA splicing mechanisms followed by a discussion of disease-associated errors, with an emphasis on recently described mutations that have provided new insights into splicing regulation. We also discuss emerging strategies for splicing-modulating therapy.
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610-3610 USA.
authors.forename: Marina M
authors.initials: MM
authors.lastname: Scotti
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610-3610 USA.
authors.forename: Maurice S
authors.initials: MS
authors.lastname: Swanson
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015316:Genetic Therapy; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017381:Spliceosomes / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger