RBFOX3/NeuN Products

Rbfox3 (also known as Fox-3, Fox1 homolog C, Hrnbp3, and D11Bwg0517e) is one of three mammalian members of the RNA-binding protein Rbfox gene family, all of which are involved in regulating alternative RNA splicing. Originally identified as an epitope, NeuN is located within the N-terminal region (6-15 amino acids) of Rbfox3. Rbfox family members are highly conserved, having a single RNA recognition motif (RRM)-type RNA binding domain (RBD) near the center of the protein sequence. The RBD amino acid (aa) sequence is identical between members, Rbfox1 and Rbfox2, with 4 differences within the 77 aa domain of Rbfox3. The fox3 gene is comprised of 15 exons in humans, 11 exons in rat, with 3 variants in mouse containing 14 exons and another 3 variants containing 15 exons. The Rbfox3 protein is highly conserved across human, mouse, and rat with 98.9% sequence identity between mouse (isoform I) and rat and 83.9% sequence identity between mouse (isoform I) and human. The expression of Rbfox3/NeuN is restricted to the nervous system and has widely been used in stroke research. It is recognized as a marker of mature neuronal cell types in the spinal cord, cerebral cortex, hippocampus, dorsal thalamus, caudate/putamen, and cerebellum. NeuN has been shown to bind DNA and is predominantly nuclear. Differences in immunoreactivity have been reported between Rbfox3/NeuN subtypes in which the 46kDa is mainly found in the nucleus whereas the 48kDa form is primarily distributed in the cytoplasm (1,2).

Rbfox proteins participate in regulation of alternative splicing between family members as well as in autoregulation. While the breadth of brain and muscle specific targets for alternative splicing is well established for Rbfox proteins, those specific to Rbfox3/NeuN along with its alternative splicing mechanism are less understood. Rbfox3 has been shown to regulate neuronal differentiation by alternative splicing of Numb pre-mRNA and has a role in adult neurogenesis. Dysfunctional Rbfox3/NeuN has been associated with various neurological disorders such as neurodevelopmental delay, autism spectrum disorder, Benign rolandic epilepsy (BRE), and cognitive impairments (1,2).

References

1. Duan W, Zhang YP, Hou Z, Huang C, Zhu H, Zhang CQ, Yin Q. (2016) Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator. Mol Neurobiol. 53(3):1637-1647. PMID: 25680637.

2. Su CH, D D, Tarn WY. (2018) Alternative Splicing in Neurogenesis and Brain Development. Front Mol Biosci. 5:12. PMID: 29484299