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| Status |
Public on Sep 11, 2014 |
| Title |
A global regulatory mechanism for activating an exon network required for neurogenesis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
The vertebrate and neural-specific SR-related protein nSR100/SRRM4 regulates an extensive program of alternative splicing with critical roles in nervous system development. However, the mechanism by which nSR100 controls its target exons is poorly understood. We demonstrate that nSR100-dependent neural exons are associated with a unique configuration of intronic cis-elements that promote rapid switch-like regulation during neurogenesis. A key feature of this configuration is the insertion of specialized intronic enhancers between polypyrimidine tracts and acceptor sites that bind nSR100 to potently activate exon inclusion in neural cells, while weakening 3' splice site recognition and contributing to exon skipping in non-neural cells. nSR100 further operates by forming multiple interactions with early spliceosome components bound proximal to 3' splice sites. These multifaceted interactions achieve dominance over neural exon silencing mediated by the splicing regulator PTBP1. The results thus illuminate a widespread mechanism by which a critical neural exon network is activated during neurogenesis.
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| Overall design |
RNA-Seq was used to obtain mRNA profiles of various N2A and 293T cell lines from human and mouse, respectively, to investigate the roles of nSR100, Ptbp1 and U2af65 in alternative splicing regulation. PAR-iCLIP and iCLIP experiments followed by high throughput sequencing were conducted to obtain RNA binding profiles of nSR100, PTBP1 and U2af65.
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| Contributor(s) |
Raj B, Irimia M, Braunschweig U, Sterne-Weiler T, O'Hanlon D, Lin Z, Chen GI, Easton L, Ule J, Gingras A, Eyras E, Blencowe B |
| Citation(s) |
25219497 |
| Submission date |
May 05, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Bushra Raj |
| E-mail(s) |
bushraraj@fas.harvard.edu
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| Organization name |
Harvard University
|
| Street address |
16 Divinity Avenue
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (3) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA246157 |
| SRA |
SRP041656 |
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