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| Status |
Public on Sep 01, 2015 |
| Title |
An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates |
| Organisms |
Gallus gallus; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Alternative splicing (AS) generates extensive transcriptomic and proteomic complexity. However, the functions of species- and lineage-specific splice variants are largely unknown. Here, we show that mammalian-specific skipping of exon 9 of PTBP1 alters its splicing regulatory activities and affects the inclusion levels of numerous exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity so as to facilitate activation of a brain-specific AS program. Engineered skipping of the orthologous exon in chicken cells induces a large number of mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a single exon skipping event in an RNA binding regulator directs numerous AS changes between species. The results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systems.
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| Overall design |
This study contains two sets of samples: (Set 1) mRNA profiling of human 293 cells subjected to four different conditions in two biological replicates: non-targetting control siRNA, PTBP1 and PTBP2 siRNA, PTBP1 and PTBP2 siRNA with overexpression of full-length human PTBP1, PTBP1 and PTBP2 siRNA with overexpression of exon-excluded human PTBP1. (Set 2) mRNA profiling of chicken DT40 cells with 3 genotypes in two bioligcal replicates: wildtype cells, cells with PTBP1 exon 8 (orthologous to human PTBP1 exon 9) deleted in one allele, and cells with PTBP1 exon 8 deleted in both alleles.
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| Contributor(s) |
Gueroussov S, Irimia M, Blencowe BJ |
| Citation(s) |
26293963 |
| Submission date |
Jun 08, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Serge Gueroussov |
| E-mail(s) |
serge.gueroussov@utoronto.ca
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| Organization name |
University of Toronto
|
| Department |
Molecular Genetics
|
| Lab |
Dr. Benjamin Blencowe
|
| Street address |
160 College Street, Room 1030
|
| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5S 3E1 |
| Country |
Canada |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL19005 |
Illumina HiSeq 2500 (Gallus gallus) |
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| Samples (14)
|
| GSM1705378 |
293 PTBP1 and PTBP2 double knockdown_rep2 |
| GSM1705379 |
293 PTBP1 and PTBP2 double knockdown with full-length PTBP1 overexpression_rep1 |
| GSM1705380 |
293 PTBP1 and PTBP2 double knockdown with full-length PTBP1 overexpression_rep2 |
| GSM1705381 |
293 PTBP1 and PTBP2 double knockdown with exon-excluded PTBP1 overexpression_rep1 |
| GSM1705382 |
293 PTBP1 and PTBP2 double knockdown with exon-excluded PTBP1 overexpression_rep2 |
| GSM1705383 |
dt40 wildtype_rep1 |
| GSM1705384 |
dt40 wildtype_rep2 |
| GSM1705385 |
dt40 heterozygous exon 8 deletion_rep1 |
| GSM1705386 |
dt40 heterozygous exon 8 deletion_rep2 |
| GSM1705387 |
dt40 homozygous exon 8 deletion_rep1 |
| GSM1705388 |
dt40 homozygous exon 8 deletion_rep2 |
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| Relations |
| BioProject |
PRJNA286111 |
| SRA |
SRP059242 |
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