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Genome-wide Analysis of PTB-RNA Interactions Reveals a Strategy Used by the General Splicing Repressor to Modulate Exon Inclusion or Skipping
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Recent transcriptome analysis indicates that > 90% of human genes undergo alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-characterized splicing repressor, but PTB knockdown causes both exon inclusion and skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional RNA map now reveal that dominant PTB binding near a competing constitutive splice site generally induces exon inclusion, whereas prevalent binding close to an alternative site often causes exon skipping. This positional effect was further demonstrated by disrupting or creating a PTB-binding site on minigene constructs and testing their responses to PTB knockdown or overexpression. These findings suggest a mechanism for PTB to modulate splice site competition to produce opposite functional consequences, which may be generally applicable to RNA-binding splicing factors to positively or negatively regulate alternative splicing in mammalian cells.
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“known splicing regulators, including RBFOX and PTB family members4, were associated with preferential exon inclusion or exclusion in a manner that correlated with the expression and binding location of the RBP”
From A compendium of RNA-binding motifs for decoding gene regulation (2013) · cites this paper as [34]
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Metadata
- Authors
- Xue, Y., Zhou, Y., Wu, T., Zhu, T., Ji, X., Kwon, Y.-S., Zhang, C., Yeo, G., Black, D. L., Sun, H., Fu, X.-D., & Zhang, Y.
- Affiliations
- Wuhan University (CN)
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fu, Xiang-Dong
- Zhang, Yi
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 36
- Issue
- 6
- Pages
- 996-1006
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2807993
- OpenAlex
- W1974898488
- Cited by
- 469
- References
- 43
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 23 · 2023: 28 · 2022: 25 · 2021: 19 · 2020: 22 · 2019: 15 · 2018: 35 · 2017: 24 · 2016: 25 · 2015: 34 · 2014: 44 · 2013: 35 · 2012: 43
- FWCI
- 14.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National High-tech Research and Development Program
- National Key Research and Development Program of China
- National Human Genome Research Institute (HG004659, R01HG004659)
- National Institute of General Medical Sciences (R01GM084317, GM049369, R01GM049369, GM084317)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- polypyrimidine tract-binding protein, PTB, alternative splicing, exon skipping, exon inclusion, RNA-binding proteins, splicing repressor, minigene constructs, splice site selection
- MeSH terms
- Animals, Binding Sites, Exons, HeLa Cells, Humans, Molecular Sequence Data, Protein Binding, RNA, Genome, Human, Alternative Splicing, Gene Expression Profiling, Polypyrimidine Tract-Binding Protein
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