Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks
Open accessAbstract
Alternative inclusion of exons increases the functional diversity of proteins. Among alternatively spliced exons, tissue-specific exons play a critical role in maintaining tissue identity. This raises the question of how tissue-specific protein-coding exons influence protein function. Here we investigate the structural, functional, interaction, and evolutionary properties of constitutive, tissue-specific, and other alternative exons in human. We find that tissue-specific protein segments often contain disordered regions, are enriched in posttranslational modification sites, and frequently embed conserved binding motifs. Furthermore, genes containing tissue-specific exons tend to occupy central positions in interaction networks and display distinct interaction partners in the respective tissues, and are enriched in signaling, development, and disease genes. Based on these findings, we propose that tissue-specific inclusion of disordered segments that contain binding motifs rewires interaction networks and signaling pathways. In this way, tissue-specific splicing may contribute to functional versatility of proteins and increases the diversity of interaction networks across tissues.
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Cell- and tissue-differentially regulated alternative splicing events are under-represented in folded protein domains and enriched in disordered, surface-accessible regions that embed short linear interaction motifs.
“While cell and tissue differentially-regulated AS events are significantly under-represented in functionally defined, folded domains in proteins, they are enriched in regions of protein disorder that typically are surface accessible and embed short linear interaction motifs (Buljan et al., 2012; Ellis et al., 2012; Romero et al., 2006).”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Buljan et al., 2012
Unlike longer neural exons, microexons are depleted of linear binding motifs.
“Conversely, unlike longer neural exons (Buljan et al., 2012; Ellis et al., 2012), they are depleted of linear binding motifs (Figure 5G and S5N, p<0.005, proportion tests for all comparisons).”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Buljan et al., 2012
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“Conversely, unlike longer neural exons (Buljan et al., 2012; Ellis et al., 2012), they are depleted of linear binding motifs (Figures 5G and S5N; p < 0.”
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Human long intrinsically disordered protein regions are frequent targets of positive selectionPreprint
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- Authors
- Buljan, M., Chalancon, G., Eustermann, S., Wagner, G. P., Fuxreiter, M., Bateman, A., & Babu, M. M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Buljan, Marija
- Babu, M. Madan
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 46
- Issue
- 6
- Pages
- 871-883
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3437557
- OpenAlex
- W1996572869
- Cited by
- 396
- References
- 45
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 15 · 2023: 22 · 2022: 24 · 2021: 26 · 2020: 29 · 2019: 26 · 2018: 37 · 2017: 36 · 2016: 28 · 2015: 30 · 2014: 42 · 2013: 34 · 2012: 16
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- tissue-specific splicing, alternative splicing, intrinsically disordered regions, protein-protein interaction network, binding motifs, exon inclusion, signaling pathways, disease-associated genes
- MeSH terms
- Exons, Humans, Models, Biological, Organ Specificity, Proteins, RNA Splicing, Structure-Activity Relationship, Alternative Splicing, Evolution, Molecular, Protein Interaction Maps
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