Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/69195
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Type: | Journal article |
Title: | NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2 |
Author: | Dredge, B. Jensen, K. |
Citation: | PLoS One, 2011; 6(6):e21585-1-e21585-12 |
Publisher: | Public Library of Science |
Issue Date: | 2011 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Valcarcel, J. |
Statement of Responsibility: | B. Kate Dredge and Kirk B. Jensen |
Abstract: | Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45-50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45-50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism. |
Keywords: | Hela Cells Cell Nucleus Cytoplasm Animals Humans Mice RNA-Binding Proteins DNA-Binding Proteins Nerve Tissue Proteins Nuclear Proteins Protein Isoforms Codon, Nonsense Epitope Mapping Alternative Splicing Amino Acid Sequence Base Sequence Protein Transport Molecular Sequence Data HEK293 Cells RNA Splicing Factors |
Description: | Extent: 12p. |
Rights: | © 2011 Dredge, Jensen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0021585 |
Grant ID: | http://purl.org/au-research/grants/arc/DP0559550 http://purl.org/au-research/grants/arc/DP0559550 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0021585 |
Appears in Collections: | Aurora harvest 7 Molecular and Biomedical Science publications |
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