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 Ísólfur Ólason, Mario Albrecht, H. 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 & 26 others Zenia Størling, Massimiliano Orsini, Yassen Assenov, Hagen Blankenburg, Carola Huthmacher, Fidel Ramírez, Andreas Schlicker, France Denoued, 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, L. Patthy, Janet M. Thornton, Anna Tramontano, Alfonso Valencia

Research output: Contribution to journalArticle

158 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 languageEnglish
Pages (from-to)5495-5500
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number13
DOIs
Publication statusPublished - Mar 27 2007

Fingerprint

Alternative Splicing
Complement System Proteins
Genes
Proteins
Recombinant DNA
Open Reading Frames
Protein Isoforms

Keywords

  • Function
  • Human
  • Isoforms
  • Splice
  • Structure

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Tress, M. L., Martelli, P. L., Frankish, A., Reeves, G. A., Wesselink, J. J., Yeats, C., ... 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), 5495-5500. https://doi.org/10.1073/pnas.0700800104

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

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 13, 27.03.2007, p. 5495-5500.

Research output: Contribution to journalArticle

Tress, ML, Martelli, PL, Frankish, A, Reeves, GA, Wesselink, JJ, Yeats, C, Ólason, PÍ, 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, Denoued, 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. 5495-5500. https://doi.org/10.1073/pnas.0700800104
Tress, Michael L. ; Martelli, Pier Luigi ; Frankish, Adam ; Reeves, Gabrielle A. ; Wesselink, Jan Jaap ; Yeats, Corin ; Ólason, Páll Ísólfur ; Albrecht, Mario ; Hegyi, H. ; Giorgetti, Alejandro ; Raimondo, Domenico ; Lagarde, Julien ; Laskowski, Roman A. ; López, Gonzalo ; Sadowski, Michael I. ; Watson, James D. ; Fariselli, Piero ; Rossi, Ivan ; Nagy, Alinda ; Kai, Wang ; Størling, Zenia ; Orsini, Massimiliano ; Assenov, Yassen ; Blankenburg, Hagen ; Huthmacher, Carola ; Ramírez, Fidel ; Schlicker, Andreas ; Denoued, France ; Jones, Phil ; Kerrien, Samuel ; Orchard, Sandra ; Antonarakis, Stylianos E. ; Reymond, Alexandre ; Birney, Ewan ; Brunak, Søren ; Casadio, Rita ; Guigo, Roderic ; Harrow, Jennifer ; Hermjakob, Henning ; Jones, David T. ; Lengauer, Thomas ; Orengo, Christine A. ; Patthy, L. ; Thornton, Janet M. ; Tramontano, Anna ; Valencia, Alfonso. / The implications of alternative splicing in the ENCODE protein complement. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 13. pp. 5495-5500.
@article{1e3aef254d114abbb5126f01abc7dd9e,
title = "The implications of alternative splicing in the ENCODE protein complement",
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.",
keywords = "Function, Human, Isoforms, Splice, Structure",
author = "Tress, {Michael L.} and Martelli, {Pier Luigi} and Adam Frankish and Reeves, {Gabrielle A.} and Wesselink, {Jan Jaap} and Corin Yeats and {\'O}lason, {P{\'a}ll {\'I}s{\'o}lfur} and Mario Albrecht and H. Hegyi and Alejandro Giorgetti and Domenico Raimondo and Julien Lagarde and Laskowski, {Roman A.} and Gonzalo L{\'o}pez and Sadowski, {Michael I.} and Watson, {James D.} and Piero Fariselli and Ivan Rossi and Alinda Nagy and Wang Kai and Zenia St{\o}rling and Massimiliano Orsini and Yassen Assenov and Hagen Blankenburg and Carola Huthmacher and Fidel Ram{\'i}rez and Andreas Schlicker and France Denoued and Phil Jones and Samuel Kerrien and Sandra Orchard and Antonarakis, {Stylianos E.} and Alexandre Reymond and Ewan Birney and S{\o}ren Brunak and Rita Casadio and Roderic Guigo and Jennifer Harrow and Henning Hermjakob and Jones, {David T.} and Thomas Lengauer and Orengo, {Christine A.} and L. Patthy and Thornton, {Janet M.} and Anna Tramontano and Alfonso Valencia",
year = "2007",
month = "3",
day = "27",
doi = "10.1073/pnas.0700800104",
language = "English",
volume = "104",
pages = "5495--5500",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - The implications of alternative splicing in the ENCODE protein complement

AU - Tress, Michael L.

AU - Martelli, Pier Luigi

AU - Frankish, Adam

AU - Reeves, Gabrielle A.

AU - Wesselink, Jan Jaap

AU - Yeats, Corin

AU - Ólason, Páll Ísólfur

AU - Albrecht, Mario

AU - Hegyi, H.

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 - Denoued, 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, L.

AU - Thornton, Janet M.

AU - Tramontano, Anna

AU - Valencia, Alfonso

PY - 2007/3/27

Y1 - 2007/3/27

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.

KW - Function

KW - Human

KW - Isoforms

KW - Splice

KW - Structure

UR - http://www.scopus.com/inward/record.url?scp=34248368920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248368920&partnerID=8YFLogxK

U2 - 10.1073/pnas.0700800104

DO - 10.1073/pnas.0700800104

M3 - Article

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

SN - 0027-8424

IS - 13

ER -