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| Status |
Public on May 31, 2013 |
| Title |
Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain [HITS-CLIP] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Two polypyrimidine tract RNA-binding proteins (PTBs), one near-ubiquitously expressed (Ptbp1) and another highly tissue-restricted (Ptbp2), regulate RNA in interrelated but incompletely understood ways. Ptbp1, a splicing regulator, is replaced in the brain and differentiated neuronal cell lines by Ptbp2. To define the roles of Ptbp2 in the nervous system, we generated two independent Ptbp2-null strains, unexpectedly revealing that Ptbp2 is expressed in neuronal progenitors and is essential for postnatal survival. A HITS-CLIP (high-throughput sequencing crosslinking immunoprecipitation)-generated map of reproducible Ptbp2–RNA interactions in the developing mouse neocortex, combined with results from splicing-sensitive microarrays, demonstrated that the major action of Ptbp2 is to inhibit adult-specific alternative exons by binding pyrimidine-rich sequences upstream of and/or within them. These regulated exons are present in mRNAs encoding proteins associated with control of cell fate, proliferation, and the actin cytoskeleton, suggesting a role for Ptbp2 in neurogenesis. Indeed, neuronal progenitors in the Ptbp2-null brain exhibited an aberrant polarity and were associated with regions of premature neurogenesis and reduced progenitor pools. Thus, Ptbp2 inhibition of a discrete set of adult neuronal exons underlies early brain development prior to neuronal differentiation and is essential for postnatal survival.
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| Overall design |
Eight Ptbp2 HITS-CLIP libraries generated from mouse embryonic brain (four libraries from each of two biologic replicates).
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| Contributor(s) |
Licatalosi DD, Darnell RB |
| Citation(s) |
22802532 |
| |
| Submission date |
May 31, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Donny D Licatalosi |
| Organization name |
Case Western Reserve University
|
| Lab |
Licatalosi
|
| Street address |
10900 Euclid Ave
|
| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE47567 |
Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain |
|
| Relations |
| BioProject |
PRJNA206086 |
| SRA |
SRP023497 |
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