Cited by 263RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB

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Llorian, Miriam, Schwartz, Schraga, Clark, Tyson A, Hollander, Dror, Tan, Lit-Yeen, Spellman, Rachel, Gordon, Adele, Schweitzer, Anthony C, de la Grange, Pierre, Ast, Gil, Smith, Christopher W J·2010·Nature Structural & Molecular Biology

DOI 10.1038/nsmb.1881PMC PMC2933513

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Abstract

To gain global insights into the role of the well-known repressive splicing regulator PTB, we analyzed the consequences of PTB knockdown in HeLa cells using high-density oligonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB-repressed and PTB-activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTB-activated exon to a PTB-repressed exon. Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.

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Self-citation

Authors: Llorian, M., Schwartz, S., Clark, T. A., Hollander, D., Tan, L.-Y., Spellman, R., Gordon, A., Schweitzer, A. C., de la Grange, P., Ast, G., & Smith, C. W. J.
Affiliations: University of Cambridge (GB)
Tel Aviv University (IL)
Affymetrix (United States) (US)
Institute of Cancer Research (GB)
Corresponding author: Smith, Christopher W J
ORCID: Llorian, Miriam
Schwartz, Schraga
Clark, Tyson A
Ast, Gil
Smith, Christopher W J
Venue: Nature Structural & Molecular Biology
Publisher: Springer Science and Business Media LLC
Published: 2010-08-15
Volume: 17
Issue: 9
Pages: 1114-1123
ISSN: 1545-9985 (ISSN-L)
1545-9993
DOI: 10.1038/nsmb.1881
PMC: PMC2933513
OpenAlex: W2042086006
Cited by: 263
References: 69
Citations by year: 2026: 9 · 2025: 13 · 2024: 15 · 2023: 22 · 2022: 9 · 2021: 15 · 2020: 12 · 2019: 8 · 2018: 17 · 2017: 15 · 2016: 17 · 2015: 19 · 2014: 21 · 2013: 22 · 2012: 28
FWCI: 9.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Structural & Molecular Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Wellcome Trust (077877)
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, splicing regulation, cassette exons, HeLa cells
MeSH terms: Base Sequence, Exons, HeLa Cells, Humans, Introns, Molecular Sequence Data, Alternative Splicing, Oligonucleotide Array Sequence Analysis, Silencer Elements, Transcriptional, Polypyrimidine Tract-Binding Protein

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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB

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