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RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression.

Woan-Yuh Tarn1, Hung-Che Kuo2, Hsin-I Yu2

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RNA-binding protein 4 (RBM4) regulates Numb splicing, promoting neuronal differentiation and neurite outgrowth. This study reveals RBM4

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Area of Science:

  • Molecular Biology
  • Neuroscience
  • Gene Regulation

Background:

  • RNA-binding protein 4 (RBM4) is involved in cell differentiation and neurogenesis.
  • Alternative pre-mRNA splicing is crucial for tissue-specific gene function.
  • Numb is a key cell-fate determination gene implicated in neurogenesis.

Purpose of the Study:

  • To investigate the role of RBM4 in regulating Numb splicing during neural differentiation.
  • To determine how RBM4-mediated Numb splicing impacts neuronal cell fate and development.

Main Methods:

  • Utilized mouse embryonal carcinoma P19 cells as a neural differentiation model.
  • Performed RBM4 knockdown and ectopic expression experiments.
  • Employed splicing reporter minigene assays and analyzed Numb pre-mRNA splicing in vivo.
  • Assessed expression of the proneural gene Mash1 and neurite outgrowth in cortical neurons.

Main Results:

  • RBM4 expression correlated with altered Numb splicing isoforms during neural differentiation.
  • RBM4 knockdown affected Numb exon 3 inclusion and exon 9 exclusion, impacting Mash1 expression.
  • RBM4 promoted specific Numb isoforms that enhanced Mash1 expression, neuronal differentiation, and neurite outgrowth.

Conclusions:

  • RBM4 plays a critical role in modulating Numb exon selection during neurogenesis.
  • RBM4-dependent Numb isoforms are essential for promoting neuronal differentiation and neurite outgrowth.
  • RBM4 is a key regulator of neural development through its control of alternative splicing.