Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors

Hwang, I., Cao, D., Na, Y., Kim, D. Y., Zhang, T., Yao, J., Oh, H., Hu, J., Zheng, H., Yao, Y., Paik, J. (March 2018) Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors. Stem Cell Reports, 10 (4). pp. 1208-1221. ISSN 2213-6711 (Electronic)2213-6711 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/29606613
DOI: 10.1016/j.stemcr.2018.02.013

Abstract

Loss of a cell's ability to terminally differentiate because of mutations is a selected genetic event in tumorigenesis. Genomic analyses of low-grade glioma have reported recurrent mutations of far upstream element-binding protein 1 (FUBP1). Here, we show that FUBP1 expression is dynamically regulated during neurogenesis and that its downregulation in neural progenitors impairs terminal differentiation and promotes tumorigenesis collaboratively with expression of IDH1(R132H). Mechanistically, collaborative action between SRRM4 and FUBP1 is necessary for mini-exon splicing of the neurospecific LSD1+8a isoform. LSD1+8a was downregulated upon loss of FUBP1 in neural progenitors, thereby impairing terminal neuronal differentiation and maturation. Reinforcing LSD1+8a expression in FUBP1-downregulated neural progenitors restored terminal differentiation and suppressed tumorigenesis; hence, LSD1+8a is an obligatory effector of FUBP1-dependent neuronal differentiation. These findings establish a direct role for FUBP1 in neuronal differentiation and also explain its tumor-suppressor function in the nervous system.

Item Type: Paper
Uncontrolled Keywords: Fubp1 Lsd1 differentiation glioma neural stem cell oligodendroglioma splicing
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
CSHL Authors:
Communities: CSHL labs > Zheng lab
Depositing User: Matt Covey
Date: 21 March 2018
Date Deposited: 05 Apr 2018 15:53
Last Modified: 22 May 2019 15:08
PMCID: PMC5998560
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36347

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