title: The alternative heart: impact of alternative splicing in heart disease.
abstract: Alternative splicing is the main driver of protein diversity and allows the production of different proteins from each gene in the genome. Changes in exon exclusion, intron retention or the use of alternative splice sites can alter protein structure, localisation, regulation and function. In the heart, alternative splicing of sarcomeric genes, ion channels and cell signalling proteins can lead to cardiomyopathies, arrhythmias and other pathologies. Also, a number of inherited conditions and heart-related diseases develop as a result of mutations affecting splicing. Here, we review the impact that changes in alternative splicing have on individual genes and on whole biological processes associated with heart disease. We also discuss promising therapeutic tools based on the manipulation of alternative splicing.
authors.affiliation: Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro 3, 28029, Madrid, Spain, elara@cnic.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lara-Pezzi
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Salinero
authors.forename: Alberto
authors.initials: A
authors.lastname: Gatto
authors.forename: Pablo
authors.initials: P
authors.lastname: García-Pavía
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D020013:Calcium Signaling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels