title: Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development.
abstract: 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.
authors: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Kee K
authors: KK
authors: Kim
authors: Joseph
authors: J
authors: Nam
authors: Yoh-Suke
authors: YS
authors: Mukouyama
authors: Sachiyo
authors: S
authors: Kawamoto
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002642:Chick Embryo; D004268:DNA-Binding Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D054259:Neural Tube / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C106293:Numb protein, mouse; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger