title: Alternative Splicing May Not Be the Key to Proteome Complexity.
abstract: Alternative splicing is commonly believed to be a major source of cellular protein diversity. However, although many thousands of alternatively spliced transcripts are routinely detected in RNA-seq studies, reliable large-scale mass spectrometry-based proteomics analyses identify only a small fraction of annotated alternative isoforms. The clearest finding from proteomics experiments is that most human genes have a single main protein isoform, while those alternative isoforms that are identified tend to be the most biologically plausible: those with the most cross-species conservation and those that do not compromise functional domains. Indeed, most alternative exons do not seem to be under selective pressure, suggesting that a large majority of predicted alternative transcripts may not even be translated into proteins.
authors.affiliation: Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tress
authors.affiliation: Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain; Human Genetics Department, Sandhu Group, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Federico
authors.initials: F
authors.lastname: Abascal
authors.affiliation: Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain; National Bioinformatics Institute (INB), Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain. Electronic address: valencia@cnio.es.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D005091:Exons; D020033:Protein Isoforms / Q000235:genetics; D020543:Proteome / Q000235:genetics*; D040901:Proteomics
chemical_list: D020033:Protein Isoforms; D020543:Proteome
keywords: RNA-seq; alternative splicing; dominant isoforms; functional isoforms; homology; proteomics