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

12Citations
Citations of this article
57Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

Vuong, J. K., Lin, C. H., Zhang, M., Chen, L., Black, D. L., & Zheng, S. (2016). PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing. Cell Reports, 17(10), 2766–2775. https://doi.org/10.1016/j.celrep.2016.11.034

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free