RESEARCH ARTICLE Alternatively Spliced Homologous Exons Have Ancient Origins and Are Highly Expressed at the Protein Level Federico Abascal1, Iakes Ezkurdia2, Juan Rodriguez-Rivas1, Jose Manuel Rodriguez3, Angela del Pozo4, Jesús Vázquez5, Alfonso Valencia1,3*, Michael L. Tress1* 1 Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, 2 Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, 3 National Bioinformatics Institute (INB), Spanish National Cancer Research Centre (CNIO), Madrid, Spain, 4 Instituto de Genetica Medica y Molecular, Hospital Universitario La Paz, Madrid, Spain, 5 Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid, Spain *
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[email protected] (MLT) OPEN ACCESS Abstract Citation: Abascal F, Ezkurdia I, Rodriguez-Rivas J, Alternative splicing of messenger RNA can generate a wide variety of mature RNA tran- Rodriguez JM, del Pozo A, Vázquez J, et al. (2015) Alternatively Spliced Homologous Exons Have scripts, and these transcripts may produce protein isoforms with diverse cellular functions. Ancient Origins and Are Highly Expressed at the While there is much supporting evidence for the expression of alternative transcripts, the Protein Level. PLoS Comput Biol 11(6): e1004325. same is not true for the alternatively spliced protein products. Large-scale mass spectrosco- doi:10.1371/journal.pcbi.1004325 py experiments have identified evidence of alternative splicing at the protein level, but with Editor: Lukas Käll, Royal Institute of Technology, conflicting results. Here we carried out a rigorous analysis of the peptide evidence from SWEDEN eight large-scale proteomics experiments to assess the scale of alternative splicing that is Received: December 16, 2014 detectable by high-resolution mass spectroscopy.