The implications of alternative splicing in the ENCODE protein complement.
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.
Tress
Michael L
ML
Structural Computational Biology Programme, Spanish National Cancer Research Centre, E-28029 Madrid, Spain. mtress@cnio.es
Martelli
Pier Luigi
PL
Frankish
Adam
A
Reeves
Gabrielle A
GA
Wesselink
Jan Jaap
JJ
Yeats
Corin
C
Olason
Páll Isólfur
PI
Albrecht
Mario
M
Hegyi
Hedi
H
Giorgetti
Alejandro
A
Raimondo
Domenico
D
Lagarde
Julien
J
Laskowski
Roman A
RA
López
Gonzalo
G
Sadowski
Michael I
MI
Watson
James D
JD
Fariselli
Piero
P
Rossi
Ivan
I
Nagy
Alinda
A
Kai
Wang
W
Størling
Zenia
Z
Orsini
Massimiliano
M
Assenov
Yassen
Y
Blankenburg
Hagen
H
Huthmacher
Carola
C
Ramírez
Fidel
F
Schlicker
Andreas
A
Denoeud
France
F
Jones
Phil
P
Kerrien
Samuel
S
Orchard
Sandra
S
Antonarakis
Stylianos E
SE
Reymond
Alexandre
A
Birney
Ewan
E
Brunak
Søren
S
Casadio
Rita
R
Guigo
Roderic
R
Harrow
Jennifer
J
Hermjakob
Henning
H
Jones
David T
DT
Lengauer
Thomas
T
Orengo
Christine A
CA
Patthy
László
L
Thornton
Janet M
JM
Tramontano
Anna
A
Valencia
Alfonso
A
D017398:Alternative Splicing; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D020407:Internet; D008958:Models, Molecular; D011487:Protein Conformation; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D012322:RNA Precursors; D012326:RNA Splicing
D020033:Protein Isoforms; D021382:Protein Sorting Signals; D011506:Proteins; D012322:RNA Precursors