Cited by 470RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

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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Xue, Yuanchao, Zhou, Yu, Wu, Tongbin, Zhu, Tuo, Ji, Xiong, Kwon, Young-Soo, Zhang, Chao, Yeo, Gene +4 more·2009·Molecular Cell

Abstract

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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Crossref · 10.1016/j.molcel.2009.12.003

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  • Known splicing regulators, including RBFOX and PTB family members, were associated with preferential exon inclusion or exclusion in a manner correlated with the expression and binding location of the RBP.

    “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”

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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
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2009-12
Volume
36
Issue
6
Pages
996-1006
ISSN
1097-2765 (ISSN-L)
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
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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