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.
N1 - Funding Information:
We thank M. Hallegger, N. McGlincy and J. Ule for comments on the manuscript. This work was supported by a Wellcome Trust programme grant to C.W.J.S. (077877) and European Commission grant EURASNET-LSHG-CT-2005-518238 (C.W.J.S. and G.A.). G.A. is supported by grants from the Israel Science Foundation (ISF 61/09), Joint Germany-Israeli Research Program (ca-139), Deutsche-Israel Project (DIP MI-1317), the Israel Cancer Association and the Israel Cancer Research Foundation (ICRF). P.G. was supported by the Association Française contre les Myopathies and European Commission grant EURASNET-LSHG-CT-2005-518238. S.S. and D.H. are fellows of the Edmond J. Safra bioinformatics program at Tel Aviv University. This work was performed in partial fulfillment of the requirements for a PhD degree of S.S. and D.H., Sackler Faculty of Medicine, Tel Aviv University, Israel.
PY - 2010/9
Y1 - 2010/9
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77956342570&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1881
DO - 10.1038/nsmb.1881
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AN - SCOPUS:77956342570
SN - 1545-9993
VL - 17
SP - 1114
EP - 1123
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 9
ER -