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

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 cross-linking 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.

Pubmed ID: 22802532


  • Licatalosi DD
  • Yano M
  • Fak JJ
  • Mele A
  • Grabinski SE
  • Zhang C
  • Darnell RB


Genes & development

Publication Data

July 15, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: K99GM95713
  • Agency: NINDS NIH HHS, Id: NS34389
  • Agency: NINDS NIH HHS, Id: NS40955
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alternative Splicing
  • Animals
  • Brain
  • Cell Differentiation
  • Exons
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Mice
  • Mice, Mutant Strains
  • Nerve Tissue Proteins
  • Neural Stem Cells
  • Polypyrimidine Tract-Binding Protein
  • RNA, Messenger