The implications of alternative splicing in the ENCODE protein complement

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

doi:10.1073/pnas.0700800104

The implications of alternative splicing in the ENCODE protein complement

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

163 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	13
Pages (from-to)	5495-500
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.0700800104
Publication status	Published - 2007
Externally published	Yes

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Tress, M. L., Martelli, P. L., Frankish, A., Reeves, G. A., Wesselink, J. J., Yeats, C., Olason, P. I., Albrecht, M., Hegyi, H., Giorgetti, A., Raimondo, D., Lagarde, J., Laskowski, R. A., López, G., Sadowski, M. I., Watson, J. D., Fariselli, P., Rossi, I., Nagy, A., ... Valencia, A. (2007). The implications of alternative splicing in the ENCODE protein complement. Proceedings of the National Academy of Sciences of the United States of America, 104(13), 5495-500. https://doi.org/10.1073/pnas.0700800104

Tress, ML, Martelli, PL, Frankish, A, Reeves, GA, Wesselink, JJ, Yeats, C, Olason, PI, Albrecht, M, Hegyi, H, Giorgetti, A, Raimondo, D, Lagarde, J, Laskowski, RA, López, G, Sadowski, MI, Watson, JD, Fariselli, P, Rossi, I, Nagy, A, Kai, W, Størling, Z, Orsini, M, Assenov, Y, Blankenburg, H, Huthmacher, C, Ramírez, F, Schlicker, A, Denoeud, F, Jones, P, Kerrien, S, Orchard, S, Antonarakis, SE, Reymond, A, Birney, E, Brunak, S, Casadio, R, Guigo, R, Harrow, J, Hermjakob, H, Jones, DT, Lengauer, T, Orengo, CA, Patthy, L, Thornton, JM, Tramontano, A & Valencia, A 2007, 'The implications of alternative splicing in the ENCODE protein complement', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 13, pp. 5495-500. https://doi.org/10.1073/pnas.0700800104

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abstract = "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.",

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AU - Martelli, Pier Luigi

AU - Frankish, Adam

AU - Reeves, Gabrielle A

AU - Wesselink, Jan Jaap

AU - Yeats, Corin

AU - Olason, Páll Isólfur

AU - Albrecht, Mario

AU - Hegyi, Hedi

AU - Giorgetti, Alejandro

AU - Raimondo, Domenico

AU - Lagarde, Julien

AU - Laskowski, Roman A

AU - López, Gonzalo

AU - Sadowski, Michael I

AU - Watson, James D

AU - Fariselli, Piero

AU - Rossi, Ivan

AU - Nagy, Alinda

AU - Kai, Wang

AU - Størling, Zenia

AU - Orsini, Massimiliano

AU - Assenov, Yassen

AU - Blankenburg, Hagen

AU - Huthmacher, Carola

AU - Ramírez, Fidel

AU - Schlicker, Andreas

AU - Denoeud, France

AU - Jones, Phil

AU - Kerrien, Samuel

AU - Orchard, Sandra

AU - Antonarakis, Stylianos E

AU - Reymond, Alexandre

AU - Birney, Ewan

AU - Brunak, Søren

AU - Casadio, Rita

AU - Guigo, Roderic

AU - Harrow, Jennifer

AU - Hermjakob, Henning

AU - Jones, David T

AU - Lengauer, Thomas

AU - Orengo, Christine A

AU - Patthy, László

AU - Thornton, Janet M

AU - Tramontano, Anna

AU - Valencia, Alfonso

PY - 2007

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N2 - 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.

AB - 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.

U2 - 10.1073/pnas.0700800104

DO - 10.1073/pnas.0700800104

M3 - Journal article

C2 - 17372197

SN - 0027-8424

VL - 104

SP - 5495

EP - 5500

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 13

ER -

The implications of alternative splicing in the ENCODE protein complement

Abstract

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