Chinese Academy of
Sciences Protein
Science core facility
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IBP Seminar:Genome-wide analysis of PTB binding reveals a strategy used by the general splicing repressor to positively or negatively regulate alternative splicing in mammalian cells. August 11, 2009 |
Author: |
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Update time: |
2009-07-31 |
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what: |
Genome-wide analysis of PTB binding reveals a strategy used by the general splicing repressor to positively or negatively regulate alternative splicing in mammalian cells |
who: |
Yi Zhang, Ph.D., Professor
Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University |
when: |
Tuesday, August 11, 2009 15:30 p.m. |
where: |
Lecture Hall in Library, Institute of Biophysics |
Host: |
Ying Wu, Professor |
More Information: |
Recent transcriptome analysis indicates that >90% of human genes undergoes alternative splicing, underscoring the contribution of differential RNA processing to the structural and functional diversity of the proteome in higher eukaryotic cells. The polypyrimidine tract binding protein PTB has been characterized as a general splicing repressor in vitro, but PTB knockdown by RNAi causes both exon inclusion and skipping in vivo. By genome-wide mapping of PTB-RNA interactions and construction of a functional RNA map, we now provide a plausible mechanism for this paradox. We found that PTB binding sites are frequently associated with both the 5’ and 3’ splice sites regardless of whether or not those sites are involved in alternative splicing. About one third of PTB binding events are linked to regulated splicing in the human genome where dominant binding near a competing constitutive splice site generally induces exoninclusion whereas prevalent binding close to an alternative site often causes exon skipping. We further demonstrated this position-dependent effect by disrupting or creating a PTB binding site on minigene constructs. These findings suggest a novel mechanism for PTB to modulate splice site competition to produce opposite functional outcomes, which may be generally applicable to RNA binding splicing suppressors to positively or negatively regulate alternative splicing in mammalian cells.
Zhang Yi.pdf |
From: |
Scientific Administration Office of IBP, July 24, 2009 |
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