Research Paper Volume 13, Issue 2 pp 2330—2347

CPEB3 regulates neuron-specific alternative splicing and involves neurogenesis gene expression

Wenrui Qu1, , Hongjuan Jin2, , Bing-Peng Chen3, , Jun Liu1, *, , Rui Li1, *, , Wenlai Guo1, *, , Heng Tian1, *, ,

  • 1 Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, Jilin Province, China
  • 2 Department of Plastic and Reconstructive Surgery, The First Hospital of Jilin University, Changchun, China
  • 3 Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, Jilin Province, China
* Equal contribution

Received: June 27, 2020       Accepted: October 27, 2020       Published: December 9, 2020
How to Cite

Copyright: © 2020 Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


In the mammalian brain, alternative pre-mRNA splicing is a fundamental mechanism that modifies neuronal function dynamically where secretion of different splice variants regulates neurogenesis, development, pathfinding, maintenance, migration, and synaptogenesis. Sequence-specific RNA-Binding Protein CPEB3 has distinctive isoform-distinct biochemical interactions and neuronal development assembly roles. Nonetheless, the mechanisms moderating splice isoform options remain unclear. To establish the modulatory trend of CPEB3, we cloned and excessively expressed CPEB3 in HT22 cells. We used RNA-seq to analyze CPEB3-regulated alternative splicing on control and CPEB3-overexpressing cells. Consequently, we used iRIP-seq to identify CPEB-binding targets. We additionally validated CPEB3-modulated genes using RT-qPCR. CPEB3 overexpression had insignificant effects on gene expression in HT22 cells. Notably, CPEB3 partially modulated differential gene splicing enhanced in the modulation of neural development, neuron cycle, neurotrophin, synapse, and specific development pathway, implying an alternative splicing regulatory mechanism associated with neurogenesis. Moreover, qRT-PCR verified the CPEB3-modulated transcription of neurogenesis genes LCN2 and NAV2, synaptogenesis gene CYLD, as well as neural development gene JADE1. Herein, we established that CPEB3 is a critical modulator of alternative splicing in neurogenesis, which remarkably enhances the current understanding of the CPEB3 mediated alternative pre-mRNA splicing.


RBP: RNA-binding proteins; CPEB: cytoplasmic polyadenylation element-binding protein; PRP: plasticity-related protein; AS: alternative splicing; PSD95: postsynaptic density protein 95; FPKM: fragments/kilobase of exon model per million fragments mapped; LCN2: Lipocalin-2; SAA3: serum amyloid A3; DEGs: differentially expressed genes; A3SS: alternative 3’ splice site; A5SS: alternative 5’splice site; ES: exons skipping; CE: cassette exon; CYLD: cylindromatosis; NAV2: neuron navigator 2; TRAF6: tumor necrosis factor receptor-associated factor 6.