Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing

Xinping Yang, Jasmin Coulombe-Huntington, Shuli Kang, Gloria M. Sheynkman, Tong Hao, Aaron Richardson, Song Sun, Fan Yang, Yun A. Shen, Ryan R. Murray, Kerstin Spirohn, Bridget E. Begg, Miquel Duran-Frigola, Andrew MacWilliams, Samuel J. Pevzner, Quan Zhong, Shelly A. Trigg, Stanley Tam, Lila Ghamsari, Nidhi Sahni & 18 others Song Yi, Maria D. Rodriguez, Dawit Balcha, Guihong Tan, Michael Costanzo, Brenda Andrews, Charles Boone, Xianghong J. Zhou, Kourosh Salehi-Ashtiani, Benoit Charloteaux, Alyce A. Chen, Michael A. Calderwood, Patrick Aloy, Frederick P. Roth, David E. Hill, Lilia M. Iakoucheva, Yu Xia, Marc Vidal

    Research output: Contribution to journalArticle

    Abstract

    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").

    Original languageEnglish (US)
    Pages (from-to)805-817
    Number of pages13
    JournalCell
    Volume164
    Issue number4
    DOIs
    StatePublished - Feb 11 2016

    Fingerprint

    Alternative Splicing
    Protein Isoforms
    Proteins
    Proteomics
    Open Reading Frames
    Genes
    Tissue

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Yang, X., Coulombe-Huntington, J., Kang, S., Sheynkman, G. M., Hao, T., Richardson, A., ... Vidal, M. (2016). Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell, 164(4), 805-817. https://doi.org/10.1016/j.cell.2016.01.029

    Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. / Yang, Xinping; Coulombe-Huntington, Jasmin; Kang, Shuli; Sheynkman, Gloria M.; Hao, Tong; Richardson, Aaron; Sun, Song; Yang, Fan; Shen, Yun A.; Murray, Ryan R.; Spirohn, Kerstin; Begg, Bridget E.; Duran-Frigola, Miquel; MacWilliams, Andrew; Pevzner, Samuel J.; Zhong, Quan; Trigg, Shelly A.; Tam, Stanley; Ghamsari, Lila; Sahni, Nidhi; Yi, Song; Rodriguez, Maria D.; Balcha, Dawit; Tan, Guihong; Costanzo, Michael; Andrews, Brenda; Boone, Charles; Zhou, Xianghong J.; Salehi-Ashtiani, Kourosh; Charloteaux, Benoit; Chen, Alyce A.; Calderwood, Michael A.; Aloy, Patrick; Roth, Frederick P.; Hill, David E.; Iakoucheva, Lilia M.; Xia, Yu; Vidal, Marc.

    In: Cell, Vol. 164, No. 4, 11.02.2016, p. 805-817.

    Research output: Contribution to journalArticle

    Yang, X, Coulombe-Huntington, J, Kang, S, Sheynkman, GM, Hao, T, Richardson, A, Sun, S, Yang, F, Shen, YA, Murray, RR, Spirohn, K, Begg, BE, Duran-Frigola, M, MacWilliams, A, Pevzner, SJ, Zhong, Q, Trigg, SA, Tam, S, Ghamsari, L, Sahni, N, Yi, S, Rodriguez, MD, Balcha, D, Tan, G, Costanzo, M, Andrews, B, Boone, C, Zhou, XJ, Salehi-Ashtiani, K, Charloteaux, B, Chen, AA, Calderwood, MA, Aloy, P, Roth, FP, Hill, DE, Iakoucheva, LM, Xia, Y & Vidal, M 2016, 'Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing', Cell, vol. 164, no. 4, pp. 805-817. https://doi.org/10.1016/j.cell.2016.01.029
    Yang X, Coulombe-Huntington J, Kang S, Sheynkman GM, Hao T, Richardson A et al. Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell. 2016 Feb 11;164(4):805-817. https://doi.org/10.1016/j.cell.2016.01.029
    Yang, Xinping ; Coulombe-Huntington, Jasmin ; Kang, Shuli ; Sheynkman, Gloria M. ; Hao, Tong ; Richardson, Aaron ; Sun, Song ; Yang, Fan ; Shen, Yun A. ; Murray, Ryan R. ; Spirohn, Kerstin ; Begg, Bridget E. ; Duran-Frigola, Miquel ; MacWilliams, Andrew ; Pevzner, Samuel J. ; Zhong, Quan ; Trigg, Shelly A. ; Tam, Stanley ; Ghamsari, Lila ; Sahni, Nidhi ; Yi, Song ; Rodriguez, Maria D. ; Balcha, Dawit ; Tan, Guihong ; Costanzo, Michael ; Andrews, Brenda ; Boone, Charles ; Zhou, Xianghong J. ; Salehi-Ashtiani, Kourosh ; Charloteaux, Benoit ; Chen, Alyce A. ; Calderwood, Michael A. ; Aloy, Patrick ; Roth, Frederick P. ; Hill, David E. ; Iakoucheva, Lilia M. ; Xia, Yu ; Vidal, Marc. / Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. In: Cell. 2016 ; Vol. 164, No. 4. pp. 805-817.
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