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Elife. 2014;3:e01201. doi: 10.7554/eLife.01201. Epub 2014 Jan 21.

The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation.

Author information

1
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
2
Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, United States.
3
Department of Biochemistry, West Virginia University, School of Medicine, Morgantown, United States.
4
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States.
5
Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.

Abstract

We show that the splicing regulator PTBP2 controls a genetic program essential for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to degeneration of these tissues over the first three postnatal weeks, a time when the normal cortex expands and develops mature circuits. Cultured Ptbp2(-/-) neurons exhibit the same initial viability as wild type, with proper neurite outgrowth and marker expression. However, these mutant cells subsequently fail to mature and die after a week in culture. Transcriptome-wide analyses identify many exons that share a pattern of mis-regulation in the mutant brains, where isoforms normally found in adults are precociously expressed in the developing embryo. These transcripts encode proteins affecting neurite growth, pre- and post-synaptic assembly, and synaptic transmission. Our results define a new genetic regulatory program, where PTBP2 acts to temporarily repress expression of adult protein isoforms until the final maturation of the neuron. DOI: http://dx.doi.org/10.7554/eLife.01201.001.

KEYWORDS:

RNA binding protein; alternative splicing; gene regulation; neuronal development

PMID:
24448406
PMCID:
PMC3896118
DOI:
10.7554/eLife.01201
[Indexed for MEDLINE]
Free PMC Article

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