Crossregulation and Functional Redundancy between the Splicing Regulator PTB and Its Paralogs nPTB and ROD1
Open accessAbstract
Among the targets of the repressive splicing regulator, polypyrimidine tract binding protein (PTB) is its own pre-mRNA, where PTB-induced exon 11 skipping produces an RNA substrate for nonsense-mediated decay (NMD). To identify additional PTB-regulated alternative splicing events, we used quantitative proteomic analysis of HeLa cells after knockdown of PTB. Apart from loss of PTB, the only change was upregulation of the neuronally restricted nPTB, resulting from decreased skipping of nPTB exon 10, a splicing event that leads to NMD of nPTB mRNA. Compared with knockdown of PTB alone, simultaneous knockdown of PTB and nPTB led to larger changes in alternative splicing of known and newly identified PTB-regulated splicing events. Strikingly, the hematopoietic PTB paralog ROD1 also switched from a nonproductive splicing pathway upon PTB/nPTB knockdown. Our data indicate crossregulation between PTB and its paralogs via nonproductive alternative splicing and a large degree of functional overlap between PTB and nPTB.
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Repression of Ptbp2 exon 10 by PTBP1 leads to nonsense-mediated mRNA decay of the Ptbp2 transcript and prevents its expression in PTBP1+ cells.
“The repression of exon 10 leads to nonsense-mediated mRNA decay (NMD) of the Ptbp2 transcript and prevents its expression in PTBP1+ cells15,20,21.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [21]
The mutually exclusive expression pattern of SLM1 and SLM2 is enforced by their cross-regulation via alternative splicing coupled with NMD.
“The mutually exclusive expression pattern of SLM1 and SLM2 is enforced by their cross-regulation via alternative splicing coupled with NMD, as seen with other paralogous pairs of RNA-binding proteins15,20,21,49,53,85,86.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [21]
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References 68 · Cited by 313
Research works printed but not linked: 1
- Gooding C. Roberts G.C. Smith C.W. Role of an inhibitory pyrimidine element and polypyrimidine tract binding protein in repression of a regulated alpha-tropomyosin exon RNA 4 1998 85 100 9436911 PMC1369599
- Authors
- Spellman, R., Llorian, M., & Smith, C. W. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Smith, Christopher W.J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 27
- Issue
- 3
- Pages
- 420-434
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC1940037
- OpenAlex
- W2100939507
- Cited by
- 313
- References
- 68
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 16 · 2023: 20 · 2022: 13 · 2021: 10 · 2020: 15 · 2019: 11 · 2018: 20 · 2017: 11 · 2016: 17 · 2015: 18 · 2014: 29 · 2013: 8 · 2012: 25
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (059879, 077877)
- Medical Research Council
- 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, alternative splicing, nonsense-mediated mRNA decay, exon skipping, pre-mRNA splicing regulation, protein paralogs, functional redundancy, HeLa cells
- MeSH terms
- Cells, Cultured, Exons, Gene Expression Regulation, HeLa Cells, Humans, Neurons, RNA Processing, Post-Transcriptional, RNA, Messenger, Electrophoresis, Gel, Two-Dimensional, RNA-Binding Proteins, Alternative Splicing, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Smooth Muscle, Polypyrimidine Tract-Binding Protein
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