The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“PTB, a regulator of alternative splicing (Llorian et al., 2010), was the most highly connected protein to both α-synuclein and tau in the ECII network.”
From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Llorian et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
Shapiro, M. B., & Senapathy, P. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.17.7155 · Cited by 2,313
Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing Signals
Yeo, G. W.-M., & Burge, C. B. (2004) · Journal of Computational Biology · doi:10.1089/1066527041410418 · Cited by 2,042
Makeyev, E. V., Zhang, J., Carrasco, M. A., & Maniatis, T. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.015 · Cited by 1,395
Understanding alternative splicing: towards a cellular code
Matlin, A. J., Clark, F., & Smith, C. W. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1645 · Cited by 1,299
Self-citationMechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284
HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
David, C. J., Chen, M., Assanah, M., Canoll, P., & Manley, J. L. (2010) · Nature · doi:10.1038/nature08697 · Cited by 1,179
Splicing regulation: From a parts list of regulatory elements to an integrated splicing code
Wang, Z., & Burge, C. B. (2008) · RNA · doi:10.1261/rna.876308 · Cited by 1,127
Alternative Splicing: New Insights from Global Analyses
Blencowe, B. J. (2006) · Cell · doi:10.1016/j.cell.2006.06.023 · Cited by 1,122
Barash, Y., Calarco, J. A., Gao, W., Pan, Q., Wang, X., Shai, O., Blencowe, B. J., & Frey, B. J. (2010) · Nature · doi:10.1038/nature09000 · Cited by 925
Boutz, P. L., Stoilov, P., Li, Q., Lin, C.-H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., & Black, D. L. (2007) · Genes & Development · doi:10.1101/gad.1558107 · Cited by 577
Yeo, G. W., Coufal, N. G., Liang, T. Y., Peng, G. E., Fu, X.-D., & Gage, F. H. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1545 · Cited by 572
Singh, R., Valcárcel, J., & Green, M. R. (1995) · Science · doi:10.1126/science.7761834 · Cited by 539
An RNA map predicting Nova-dependent splicing regulation
Ule, J., Stefani, G., Mele, A., Ruggiu, M., Wang, X., Taneri, B., Gaasterland, T., Blencowe, B. J., & Darnell, R. B. (2006) · Nature · doi:10.1038/nature05304 · Cited by 528
Nova regulates brain-specific splicing to shape the synapse
Ule, J., Ule, A., Spencer, J., Williams, A., Hu, J.-S., Cline, M., Wang, H., Clark, T., Fraser, C., Ruggiu, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1610 · Cited by 509
Self-citationA postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart
Kalsotra, A., Xiao, X., Ward, A. J., Castle, J. C., Johnson, J. M., Burge, C. B., & Cooper, T. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809045105 · Cited by 508
Xue, Y., Zhou, Y., Wu, T., Zhu, T., Ji, X., Kwon, Y.-S., Zhang, C., Yeo, G., Black, D. L., Sun, H., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.12.003 · Cited by 469
Structure of PTB Bound to RNA: Specific Binding and Implications for Splicing Regulation
Oberstrass, F. C., Auweter, S., Erat, M. C., Hargous, Y., Henning, A., Wenter, P., Reymond, L., Amir-Ahmady, B., Pitsch, S., Black, D. L., et al. (2005) · Science · doi:10.1126/science.1114066 · Cited by 464
Wollerton, M., Gooding, C., Wagner, E. J., García-Blanco, M. A., & Smith, C. W. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00502-1 · Cited by 409
Self-citationPolypyrimidine Tract Binding Protein Antagonizes Exon Definition
Wagner, E. J., & García-Blanco, M. A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3281-3288.2001 · Cited by 376
Mi, H., Guo, N., Kejariwal, A., & Thomas, P. D. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl869 · Cited by 372
Regulation of Fas Alternative Splicing by Antagonistic Effects of TIA-1 and PTB on Exon Definition
Izquierdo, J. M., Oró, N. M., Bonnal, S., Martínez, C., Castelo, R., Guigó, R., Bilbao, D., & Valcárcel, J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.06.015 · Cited by 364
Cancer-associated regulation of alternative splicing
Venables, J. P., Klinck, R., Koh, C., Gervais-Bird, J., Bramard, A., Inkel, L., Durand, M., Couture, S., Froehlich, U., Lapointe, E., et al. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1608 · Cited by 355
Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A., Kalsotra, A., Cooper, T. A., & Johnson, J. M. (2008) · Nature Genetics · doi:10.1038/ng.264 · Cited by 332
Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein
Sawicka, K., Bushell, M., Spriggs, K. A., & Willis, A. E. (2008) · Biochemical Society Transactions · doi:10.1042/bst0360641 · Cited by 332 · cited 1×
“as well as influencing other post-transcriptional steps in gene expressio”
BackgroundDu, H., Cline, M. S., Osborne, R. J., Tuttle, D. L., Clark, T. A., Donohue, J. P., Hall, M. P., Shiue, L., Swanson, M. S., Thornton, C. A., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1720 · Cited by 332
Self-citationSpellman, R., Llorian, M., & Smith, C. W. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.016 · Cited by 313
Self-citationJin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., & Inoue, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg089 · Cited by 311
Goren, A., Ram, O., Amit, M., Keren, H., Lev-Maor, G., Vig, I., Pupko, T., & Ast, G. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.008 · Cited by 301
Self-citationDefining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2
Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A. R., & Zhang, M. Q. (2008) · Genes & Development · doi:10.1101/gad.1703108 · Cited by 300
Discovery of tissue-specific exons using comprehensive human exon microarrays
Clark, T. A., Schweitzer, A. C., Chen, T. X., Staples, M. K., Lu, G., Wang, H., Williams, A., & Blume, J. E. (2007) · Genome biology · doi:10.1186/gb-2007-8-4-r64 · Cited by 286
Self-citationSeparable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts
Mendell, J. T., Rhys, C. M. J. A., & Dietz, H. C. (2002) · Science · doi:10.1126/science.1074428 · Cited by 258
Alternative Splicing in Colon, Bladder, and Prostate Cancer Identified by Exon Array Analysis
Thorsen, K., Sørensen, K. D., Brems-Eskildsen, A. S., Modin, C., Gaustadnes, M., Hein, A.-M. K., Kruhøffer, M., Laurberg, S., Borre, M., Wang, K., et al. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700590-mcp200 · Cited by 245
Mutation of PTB binding sites causes misregulation of alternative 3' splice site selection in vivo.
Pérez, I. C., Lin, C.-H., McAfee, J. G., & Patton, J. G. (1997) · PubMed Central · Cited by 235
The splicing regulator TIA‐1 interacts with U1‐C to promote U1 snRNP recruitment to 5′ splice sites
Förch, P., Puig, Ó., Martínez, C., Séraphin, B., & Valcárcel, J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf668 · Cited by 229
hnRNP A1 Recruited to an Exon In Vivo Can Function as an Exon Splicing Silencer
Gatto–Konczak, F. D., Olive, M., Gesnel, M.-C., & Breathnach, R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.251 · Cited by 224
Ashiya, M., & Grabowski, P. J. (1997) · PubMed · Cited by 220
Chou, M., Underwood, J. G., Nikolic, J. M., Luu, M. H. T., & Black, D. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80260-9 · Cited by 198
Comparative analysis detects dependencies among the 5′ splice-site positions
Carmel, I., Tal, S., Vig, I., & Ast, G. (2004) · RNA · doi:10.1261/rna.5196404 · Cited by 194
Self-citationSchwartz, S., Silva, J., Burstein, D., Pupko, T., Eyras, E., & Ast, G. (2007) · Genome Research · doi:10.1101/gr.6818908 · Cited by 186
Self-citationSharma, S., Kohlstaedt, L. A., Damianov, A., Rio, D. C., & Black, D. L. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1375 · Cited by 177
Pérez, I. C., McAfee, J. G., & Patton, J. G. (1997) · Biochemistry · doi:10.1021/bi9711745 · Cited by 174
Regulation of alternative 3' splice site selection by constitutive splicing factors.
Lin, C.-H., & Patton, J. G. (1995) · PubMed · Cited by 174
MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing
Sweeney, E. G., Purcell, J., Voelker, R. B., Gates, D. P., & Berglund, J. A. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp1209 · Cited by 172
Sharma, S., Falick, A. M., & Black, D. L. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.07.014 · Cited by 165
Novel modes of splicing repression by PTB
Spellman, R., & Smith, C. W. J. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.003 · Cited by 160
Self-citationHunt, S. L., & Jackson, R. J. (1999) · RNA · doi:10.1017/s1355838299981414 · Cited by 151
Lou, H. J., Helfman, D. M., Gagel, R. F., & Berget, S. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.78 · Cited by 149
Gooding, C., Clark, F., Wollerton, M., Grellscheid, S., Groom, H. C. T., & Smith, C. W. J. (2006) · Genome biology · doi:10.1186/gb-2006-7-1-r1 · Cited by 149
Self-citationRNAi-Mediated PTB Depletion Leads to Enhanced Exon Definition
Wagner, E. J., & García-Blanco, M. A. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00645-7 · Cited by 144
ASESORÍAS INNOVADORAS EN RECURSOS HUMANOS PARA LAS PYMES MEDIANTE EL USO DE LA RED DE INTERNET
ARTAVIA, N. I. V. (1969) · Revista Nacional de Administración · doi:10.22458/rna.v4i1.535 · Cited by 135
Exon repression by polypyrimidine tract binding protein
Amir-Ahmady, B., Boutz, P. L., Markovtsov, V. V., Phillips, M. L., & Black, D. L. (2005) · RNA · doi:10.1261/rna.2250405 · Cited by 118
He, X., Pool, M. D., Darcy, K. M., Lim, S. B., Auersperg, N., Coon, J. S., & Beck, W. T. (2007) · Oncogene · doi:10.1038/sj.onc.1210307 · Cited by 117
Faustino, N. A., & Cooper, T. A. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.3.879-887.2005 · Cited by 110
A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain
Rideau, A., Gooding, C., Simpson, P. J., Monie, T. P., Lorenz, M., Hüttelmaier, S., Singer, R. H., Matthews, S., Curry, S., & Smith, C. W. J. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1137 · Cited by 100
Self-citationXing, Y., Stoilov, P., Kapur, K., Han, A., Jiang, H., Shen, S., Black, D. L., & Wong, W. H. (2008) · RNA · doi:10.1261/rna.1070208 · Cited by 93
Alternative Splicing— When Two’s a Crowd
Smith, C. W. J. (2005) · Cell · doi:10.1016/j.cell.2005.09.010 · Cited by 66
Self-citationSchwartz, S., Gal-Mark, N., Kfir, N., Ram, O., Kim, E., & Ast, G. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000300 · Cited by 65
Self-citationAlternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis
Yamamoto, M. L., Clark, T. A., Gee, S. L., Kang, J.-A., Schweitzer, A. C., Wickrema, A., & Conboy, J. G. (2009) · Blood · doi:10.1182/blood-2008-05-160325 · Cited by 59
Self-citationhnRNP I/PTB can antagonize the splicing repressor activity of SRp30c
Paradis, C., Cloutier, P., Shkreta, L., Toutant, J., Klarskov, K., & Chabot, B. (2007) · RNA · doi:10.1261/rna.403607 · Cited by 57
Wang, C., Norton, J. T., Ghosh, S., Kim, J. J., Fushimi, K., Wu, J. Y., Stack, M. S., & Huang, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803682200 · Cited by 54
A Splicing Repressor Domain in Polypyrimidine Tract-binding Protein
Robinson, F., & Smith, C. W. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510578200 · Cited by 50
Self-citationReid, D. C., Chang, B. L., Gunderson, S., Sugden, L. A., Thompson, W. A., & Fairbrother, W. G. (2009) · RNA · doi:10.1261/rna.1821809 · Cited by 48
Ellis, P. D., Smith, C. W. J., & Kemp, P. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405380200 · Cited by 45
Self-citationDownstream intronic splicing enhancers
Venables, J. P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.08.012 · Cited by 33
Repression of α-actinin SM exon splicing by assisted binding of PTB to the polypyrimidine tract
Matlin, A. J., Southby, J., Gooding, C., & Smith, C. W. J. (2007) · RNA · doi:10.1261/rna.219607 · Cited by 29
Self-citationseqLogo: An R package for plotting DNA sequence logos.
Bembom, O. (2007) · Cited by 22
A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F
Coles, J. L., Hallegger, M., & Smith, C. W. J. (2008) · RNA · doi:10.1261/rna.1225209 · Cited by 16
Self-citation
Flagged first, then by citations
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 α-tropomyosin exon. RNA 4, 85–100 (1998).
Cited by
Sorted by citations
Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M., et al. (2012) · Nature · doi:10.1038/nature11112 · Cited by 4,884
Self-citationFunction of alternative splicing
Stamm, S., Ben‐Ari, S., Rafalska, I., Tang, Y., Zhang, Z., Toiber, D., Thanaraj, T. A., & Soreq, H. (2004) · Gene · doi:10.1016/j.gene.2004.10.022 · Cited by 1,398
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044
Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution
Ule, J., & Blencowe, B. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.017 · Cited by 780
Function of alternative splicing
Kelemen, O., Convertini, P., Zhang, Z., Wen, Y., Shen, M., Falaleeva, M., & Stamm, S. (2013) · Gene · doi:10.1016/j.gene.2012.07.083 · Cited by 743
Metadata
- 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
- Venue
- Nature Structural & Molecular Biology
- Published
- 2010-08-15
- Volume
- 17
- Issue
- 9
- Pages
- 1114-1123
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
