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The implications of alternative splicing in the ENCODE protein complement

2007; National Academy of Sciences; Volume: 104; Issue: 13 Linguagem: Inglês

10.1073/pnas.0700800104

1091-6490

Michael L. Tress, Pier Luigi Martelli, Adam Frankish, Gabrielle A. Reeves, Jan Jaap Wesselink, Corin Yeats, Páll ĺsólfur Ólason, Mario Albrecht, Hédi Hegyi, Alejandro Giorgetti, Domenico Raimondo, Julien Lagarde, Roman A. Laskowski, Gonzalo López, Michael I. Sadowski, James D. Watson, Piero Fariselli, Ivan Rossi, Alinda Nagy, Kai Wang, Zenia M. Størling, Massimiliano Orsini, Yassen Assenov, Hagen Blankenburg, Carola Huthmacher, Fidel Ramírez, Andreas Schlicker, France Denœud, Phil Jones, Samuel Kerrien, Sandra Orchard, Stylianos E. Antonarakis, Alexandre Reymond, Ewan Birney, Søren Brunak, Rita Casadio, Roderic Guigó, Jennifer Harrow, Henning Hermjakob, David T. Jones, Thomas Lengauer, Christine Orengo, László Patthy, Janet M. Thornton, Anna Tramontano, Alfonso Valencia,

RNA modifications and cancer

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.