Transcriptomics

Dataset Information

298

Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain [HITS-CLIP]


ABSTRACT: 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. Eight Ptbp2 HITS-CLIP libraries generated from mouse embryonic brain (four libraries from each of two biologic replicates).

ORGANISM(S): Mus musculus  

SUBMITTER: Robert B Darnell   Donny D Licatalosi 

PROVIDER: E-GEOD-47564 | ArrayExpress | 2013-05-31

SECONDARY ACCESSION(S): SRP023497GSE47564PRJNA206086

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain.

Licatalosi Donny D DD   Yano Masato M   Fak John J JJ   Mele Aldo A   Grabinski Sarah E SE   Zhang Chaolin C   Darnell Robert B RB  

Genes & development 20120701 14


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 p  ...[more]

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