title: RNA-Binding Proteins: Splicing Factors and Disease.
abstract: Pre-mRNA splicing is mediated by interactions of the Core Spliceosome and an array of accessory RNA binding proteins with cis-sequence elements. Splicing is a major regulatory component in higher eukaryotes. Disruptions in splicing are a major contributor to human disease. One in three hereditary disease alleles are believed to cause aberrant splicing. Hereditary disease alleles can alter splicing by disrupting a splicing element, creating a toxic RNA, or affecting splicing factors. One of the challenges of medical genetics is identifying causal variants from the thousands of possibilities discovered in a clinical sequencing experiment. Here we review the basic biochemistry of splicing, the mechanisms of splicing mutations, the methods for identifying splicing mutants, and the potential of therapeutic interventions.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. alger_fredericks@brown.edu.
authors.forename: Alger M
authors.initials: AM
authors.lastname: Fredericks
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. kamil_cygan@brown.edu.|Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, RI 02912, USA. kamil_cygan@brown.edu.
authors.forename: Kamil J
authors.initials: KJ
authors.lastname: Cygan
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. b.anthony.brown830@gmail.com.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Brown
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. fairbrother@brown.edu.|Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, RI 02912, USA. fairbrother@brown.edu.
authors.forename: William G
authors.initials: WG
authors.lastname: Fairbrother
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins
keywords: RNA-binding proteins; motif; splicing