Alternative splicing in human transcriptome: functional and structural influence on proteins.
Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain. We evaluated comprehensively the presumptive three-dimensional structures of the alternatively spliced products to assess the impact of alternative splicing on gene function. We found that more than half of the products encoded proteins which were involved in signal transduction, transcription and translation, and more than half of alternatively spliced regions comprised interaction sites between proteins and their binding partners, including substrates, DNA/RNA, and other proteins. Intriguingly, 67% of the alternatively spliced isoforms showed significant alterations to regions of the protein structural core, which likely resulted in large conformational change. Based on those findings, we speculate that there are a large number of cases that alternative splicing modulates protein networks through significant alteration in protein conformation.
Yura
Kei
K
Quantum Bioinformatics Team, Center for Computational Science and Engineering, Japan Atomic Energy Agency, 8-1 Umemidai, Kizu-cho, Souraku-gun, Kyoto 619-0215, Japan.
Shionyu
Masafumi
M
Hagino
Kei
K
Hijikata
Atsushi
A
Hirashima
Yoshinori
Y
Nakahara
Taku
T
Eguchi
Tatsuya
T
Shinoda
Kazuki
K
Yamaguchi
Akihiro
A
Takahashi
Ken-Ichi
K
Itoh
Takeshi
T
Imanishi
Tadashi
T
Gojobori
Takashi
T
Go
Mitiko
M
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000075244:Apelin Receptors; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000032:analysis; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry*; D020365:RNA Helicases / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000502:physiology*
C104575:APLNR protein, human; D000075244:Apelin Receptors; D018076:DNA, Complementary; D020033:Protein Isoforms; D020543:Proteome; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins; D020365:RNA Helicases