| First Author | Kim KK | Year | 2013 |
| Journal | J Cell Biol | Volume | 200 |
| Issue | 4 | Pages | 443-58 |
| PubMed ID | 23420872 | Mgi Jnum | J:195202 |
| Mgi Id | MGI:5476860 | Doi | 10.1083/jcb.201206146 |
| Citation | Kim KK, et al. (2013) Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development. J Cell Biol 200(4):443-58 |
| abstractText | Alternative premRNA splicing is a major mechanism to generate diversity of gene products. However, the biological roles of alternative splicing during development remain elusive. Here, we focus on a neuron-specific RNA-binding protein, Rbfox3, recently identified as the antigen of the widely used anti-NeuN antibody. siRNA-mediated loss-of-function studies using the developing chicken spinal cord revealed that Rbfox3 is required to promote neuronal differentiation of postmitotic neurons. Numb premRNA encoding a signaling adaptor protein was found to be a target of Rbfox3 action, and Rbfox3 repressed the inclusion of an alternative exon via binding to the conserved UGCAUG element in the upstream intron. Depleting a specific Numb splice isoform reproduced similar neuronal differentiation defects. Forced expression of the relevant Numb splice isoform was sufficient to rescue, in an isoform-specific manner, postmitotic neurons from defects in differentiation caused by Rbfox3 depletion. Thus, Rbfox3-dependent Numb alternative splicing plays an important role in the progression of neuronal differentiation during vertebrate development. |
