title: The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches.
abstract: Removal of introns from pre-mRNA precursors (pre-mRNA splicing) is a necessary step for the expression of most genes in multicellular organisms, and alternative patterns of intron removal diversify and regulate the output of genomic information. Mutation or natural variation in pre-mRNA sequences, as well as in spliceosomal components and regulatory factors, has been implicated in the etiology and progression of numerous pathologies. These range from monogenic to multifactorial genetic diseases, including metabolic syndromes, muscular dystrophies, neurodegenerative and cardiovascular diseases, and cancer. Understanding the molecular mechanisms associated with splicing-related pathologies can provide key insights into the normal function and physiological context of the complex splicing machinery and establish sound basis for novel therapeutic approaches.
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu-Fabra, Barcelona, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Daguenet
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu-Fabra, Barcelona, Spain.
authors.forename: Gwendal
authors.initials: G
authors.lastname: Dujardin
authors.affiliation: Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu-Fabra, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain juan.valcarcel@crg.eu.
authors.forename: Juan
authors.initials: J
authors.lastname: Valcárcel
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D004194:Disease / Q000235:genetics*; D005091:Exons; D006801:Humans; D007438:Introns; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000628:therapy; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger
keywords: RNA; alternative splicing; disease; mutation; spliceosome