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

RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between R...

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Autores principales: Tarn, Woan-Yuh, Kuo, Hung-Che, Yu, Hsin-I., Liu, Shin-Wu, Tseng, Ching-Tzu, Dhananjaya, Dodda, Hung, Kuan-Yang, Tu, Chi-Chiang, Chang, Shuo-Hsiu, Huang, Guo-Jen, Chiu, Ing-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865323/
https://www.ncbi.nlm.nih.gov/pubmed/27009199
http://dx.doi.org/10.1091/mbc.E15-11-0798
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author Tarn, Woan-Yuh
Kuo, Hung-Che
Yu, Hsin-I.
Liu, Shin-Wu
Tseng, Ching-Tzu
Dhananjaya, Dodda
Hung, Kuan-Yang
Tu, Chi-Chiang
Chang, Shuo-Hsiu
Huang, Guo-Jen
Chiu, Ing-Ming
author_facet Tarn, Woan-Yuh
Kuo, Hung-Che
Yu, Hsin-I.
Liu, Shin-Wu
Tseng, Ching-Tzu
Dhananjaya, Dodda
Hung, Kuan-Yang
Tu, Chi-Chiang
Chang, Shuo-Hsiu
Huang, Guo-Jen
Chiu, Ing-Ming
author_sort Tarn, Woan-Yuh
collection PubMed
description RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9–lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth.
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spelling pubmed-48653232016-07-30 RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression Tarn, Woan-Yuh Kuo, Hung-Che Yu, Hsin-I. Liu, Shin-Wu Tseng, Ching-Tzu Dhananjaya, Dodda Hung, Kuan-Yang Tu, Chi-Chiang Chang, Shuo-Hsiu Huang, Guo-Jen Chiu, Ing-Ming Mol Biol Cell Articles RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9–lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth. The American Society for Cell Biology 2016-05-15 /pmc/articles/PMC4865323/ /pubmed/27009199 http://dx.doi.org/10.1091/mbc.E15-11-0798 Text en © 2016 Tarn et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Tarn, Woan-Yuh
Kuo, Hung-Che
Yu, Hsin-I.
Liu, Shin-Wu
Tseng, Ching-Tzu
Dhananjaya, Dodda
Hung, Kuan-Yang
Tu, Chi-Chiang
Chang, Shuo-Hsiu
Huang, Guo-Jen
Chiu, Ing-Ming
RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title_full RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title_fullStr RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title_full_unstemmed RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title_short RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression
title_sort rbm4 promotes neuronal differentiation and neurite outgrowth by modulating numb isoform expression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865323/
https://www.ncbi.nlm.nih.gov/pubmed/27009199
http://dx.doi.org/10.1091/mbc.E15-11-0798
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