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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Nat Struct Mol Biol. 2010 Sep; 17(9):1114-23.NS

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.

Authors+Show Affiliations

Department of Biochemistry, University of Cambridge, Cambridge, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20711188

Citation

Llorian, Miriam, et al. "Position-dependent Alternative Splicing Activity Revealed By Global Profiling of Alternative Splicing Events Regulated By PTB." Nature Structural & Molecular Biology, vol. 17, no. 9, 2010, pp. 1114-23.
Llorian M, Schwartz S, Clark TA, et al. Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol. 2010;17(9):1114-23.
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. (2010). Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nature Structural & Molecular Biology, 17(9), 1114-23. https://doi.org/10.1038/nsmb.1881
Llorian M, et al. Position-dependent Alternative Splicing Activity Revealed By Global Profiling of Alternative Splicing Events Regulated By PTB. Nat Struct Mol Biol. 2010;17(9):1114-23. PubMed PMID: 20711188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. AU - Llorian,Miriam, AU - Schwartz,Schraga, AU - Clark,Tyson A, AU - Hollander,Dror, AU - Tan,Lit-Yeen, AU - Spellman,Rachel, AU - Gordon,Adele, AU - Schweitzer,Anthony C, AU - de la Grange,Pierre, AU - Ast,Gil, AU - Smith,Christopher W J, Y1 - 2010/08/15/ PY - 2010/01/13/received PY - 2010/06/25/accepted PY - 2010/8/17/entrez PY - 2010/8/17/pubmed PY - 2010/9/29/medline SP - 1114 EP - 23 JF - Nature structural & molecular biology JO - Nat. Struct. Mol. Biol. VL - 17 IS - 9 N2 - 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. SN - 1545-9985 UR - https://www.unboundmedicine.com/medline/citation/20711188/Position_dependent_alternative_splicing_activity_revealed_by_global_profiling_of_alternative_splicing_events_regulated_by_PTB_ L2 - http://dx.doi.org/10.1038/nsmb.1881 DB - PRIME DP - Unbound Medicine ER -