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Publication : PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing.

First Author  Vuong JK Year  2016
Journal  Cell Rep Volume  17
Issue  10 Pages  2766-2775
PubMed ID  27926877 Mgi Jnum  J:239441
Mgi Id  MGI:5828931 Doi  10.1016/j.celrep.2016.11.034
Citation  Vuong JK, et al. (2016) PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing. Cell Rep 17(10):2766-2775
abstractText  Families of alternative splicing regulators often contain multiple paralogs presumed to fulfill different functions. Polypyrimidine tract binding proteins PTBP1 and PTBP2 reprogram developmental pre-mRNA splicing in neurons, but how their regulatory networks differ is not understood. To compare their targeting, we generated a knockin allele that conditionally expresses PTBP1. Bred to a Ptbp2 knockout, the transgene allowed us to compare the developmental and molecular phenotypes of mice expressing only PTBP1, only PTBP2, or neither protein in the brain. This knockin Ptbp1 rescued a forebrain-specific, but not a pan-neuronal, Ptbp2 knockout, demonstrating both redundant and distinct roles for the proteins. Many developmentally regulated exons exhibited different sensitivities to PTBP1 and PTBP2. Nevertheless, the two paralogs displayed similar RNA binding across the transcriptome, indicating that their differential targeting does not derive from their RNA interactions, but from possible different cofactor interactions.
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