Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing

被引：387

作者：

Yang, Xinping ^{[1
,2
,3
,4
,5
]}

Coulombe-Huntington, Jasmin ^{[6
,18
]}

Kang, Shuli ^{[7
,15
]}

Sheynkman, Gloria M. ^{[1
,2
,3
,4
]}

Hao, Tong ^{[1
,2
,3
,4
]}

Richardson, Aaron ^{[1
,2
,3
,4
]}

Sun, Song ^{[8
,9
,10
,11
]}

Yang, Fan ^{[8
,9
,10
]}

Shen, Yun A. ^{[1
,2
,3
,4
]}

Murray, Ryan R. ^{[2
,3
,4
,19
]}

Spirohn, Kerstin ^{[1
,2
,3
,4
]}

Begg, Bridget E. ^{[1
,2
,3
,4
,20
]}

Duran-Frigola, Miquel ^{[12
]}

MacWilliams, Andrew ^{[2
,3
,4
,21
]}

Pevzner, Samuel J. ^{[2
,3
,4
,13
,14
]}

Zhong, Quan ^{[2
,3
,4
,22
]}

Wanamaker, Shelly A. ^{[2
,3
,4
,23
]}

Tam, Stanley ^{[2
,3
,4
,24
]}

Ghamsari, Lila ^{[2
,3
,4
,25
]}

Sahni, Nidhi ^{[1
,2
,3
,4
]}

Yi, Song ^{[1
,2
,3
,4
]}

Rodriguez, Maria D. ^{[2
,3
,4
,26
]}

Balcha, Dawit ^{[1
,2
,3
,4
]}

Tan, Guihong

Costanzo, Michael ^{[8
]}

Andrews, Brenda ^{[8
,9
]}

Boone, Charles ^{[8
,9
]}

Zhou, Xianghong J. ^{[15
]}

Salehi-Ashtiani, Kourosh ^{[2
,3
,4
,27
,28
]}

Charloteaux, Benoit ^{[1
,2
,3
,4
,29
,30
]}

Chen, Alyce A. ^{[1
,2
,3
,4
]}

Calderwood, Michael A. ^{[1
,2
,3
,4
]}

Aloy, Patrick ^{[12
,16
]}

Roth, Frederick P. ^{[1
,2
,3
,8
,9
,10
,17
]}

Hill, David E. ^{[1
,2
,3
,4
]}

Iakoucheva, Lilia M. ^{[7
]}

Xia, Yu ^{[2
,3
,6
]}

Vidal, Marc ^{[1
,2
,3
,4
]}

机构：

[1] Dana Farber Canc Inst, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[5] Southern Med Univ, Nanfang Hosp, Dept Obstet & Gynecol, Guangzhou 510515, Guangdong, Peoples R China

[6] McGill Univ, Dept Bioengn, Montreal, PQ H3A 0C3, Canada

[7] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[8] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[9] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada

[10] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada

[11] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden

[12] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain

[13] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA

[14] Boston Univ, Sch Med, Boston, MA 02118 USA

[15] Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA

[16] ICREA, Barcelona 08010, Catalonia, Spain

[17] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada

[18] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

[19] Univ Helsinki, Biomedicum Helsinki 1, FIN-00290 Helsinki, Finland

[20] MIT, Dept Biol, Cambridge, MA 02139 USA

[21] Tecan US Inc, Morrisville, NC 27560 USA

[22] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA

[23] Univ Calif San Diego, Dept Biol Sci, La Jolla, CA 92093 USA

[24] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[25] Genocea Biosci Inc, Cambridge, MA 02140 USA

[26] Cedars Sinai Med Ctr, Biomed Sci & Translat Med, Los Angeles, CA 90048 USA

[27] New York Univ Abu Dhabi, Div Sci & Math, Abu Dhabi, U Arab Emirates

[28] New York Univ Abu Dhabi, Ctr Genom & Syst Biol CGSB, Abu Dhabi, U Arab Emirates

[29] Univ Liege, Unit Anim Genom, GIGA R, B-4000 Liege, Belgium

[30] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium

来源：

CELL | 2016年 / 164卷 / 04期

基金：

瑞典研究理事会; 加拿大自然科学与工程研究理事会; 加拿大创新基金会; 美国国家科学基金会;

关键词：

OPEN READING FRAMES; OSTEOGENESIS IMPERFECTA; SCALE MAP; GENE; TRANSCRIPTOME; DISCOVERY; ISOFORMS; CLONING; COL1A2;

D O I：

10.1016/j.cell.2016.01.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms'' are functionally divergent (i.e., "functional alloforms'').

引用

页码：805 / 817

页数：13

共 43 条

[41] Alternative isoform regulation in human tissue transcriptomes [J].