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Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development

Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-s...

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Autores principales: Popovitchenko, Tatiana, Park, Yongkyu, Page, Nicholas F., Luo, Xiaobing, Krsnik, Zeljka, Liu, Yuan, Salamon, Iva, Stephenson, Jessica D., Kraushar, Matthew L., Volk, Nicole L., Patel, Sejal M., Wijeratne, H. R. Sagara, Li, Diana, Suthar, Kandarp S., Wach, Aaron, Sun, Miao, Arnold, Sebastian J., Akamatsu, Wado, Okano, Hideyuki, Paillard, Luc, Zhang, Huaye, Buyske, Steven, Kostovic, Ivica, De Rubeis, Silvia, Hart, Ronald P., Rasin, Mladen-Roko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125149/
https://www.ncbi.nlm.nih.gov/pubmed/32245946
http://dx.doi.org/10.1038/s41467-020-15412-8
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author Popovitchenko, Tatiana
Park, Yongkyu
Page, Nicholas F.
Luo, Xiaobing
Krsnik, Zeljka
Liu, Yuan
Salamon, Iva
Stephenson, Jessica D.
Kraushar, Matthew L.
Volk, Nicole L.
Patel, Sejal M.
Wijeratne, H. R. Sagara
Li, Diana
Suthar, Kandarp S.
Wach, Aaron
Sun, Miao
Arnold, Sebastian J.
Akamatsu, Wado
Okano, Hideyuki
Paillard, Luc
Zhang, Huaye
Buyske, Steven
Kostovic, Ivica
De Rubeis, Silvia
Hart, Ronald P.
Rasin, Mladen-Roko
author_facet Popovitchenko, Tatiana
Park, Yongkyu
Page, Nicholas F.
Luo, Xiaobing
Krsnik, Zeljka
Liu, Yuan
Salamon, Iva
Stephenson, Jessica D.
Kraushar, Matthew L.
Volk, Nicole L.
Patel, Sejal M.
Wijeratne, H. R. Sagara
Li, Diana
Suthar, Kandarp S.
Wach, Aaron
Sun, Miao
Arnold, Sebastian J.
Akamatsu, Wado
Okano, Hideyuki
Paillard, Luc
Zhang, Huaye
Buyske, Steven
Kostovic, Ivica
De Rubeis, Silvia
Hart, Ronald P.
Rasin, Mladen-Roko
author_sort Popovitchenko, Tatiana
collection PubMed
description Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-seq analysis of mouse neocortical polysomes, here we report translationally repressed and derepressed mRNA isoforms during neocortical neurogenesis whose orthologs include risk genes for neurodevelopmental disorders. We demonstrate that the translation of distinct mRNA isoforms of the RNA binding protein (RBP), Elavl4, in radial glia progenitors and early neurons depends on its alternative 5′ UTRs. Furthermore, 5′ UTR-driven Elavl4 isoform-specific translation depends on upstream control by another RBP, Celf1. Celf1 regulation of Elavl4 translation dictates development of glutamatergic neurons. Our findings reveal a dynamic interplay between distinct RBPs and alternative 5′ UTRs in neuronal development and underscore the risk of post-transcriptional dysregulation in co-occurring neurodevelopmental disorders.
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spelling pubmed-71251492020-04-06 Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development Popovitchenko, Tatiana Park, Yongkyu Page, Nicholas F. Luo, Xiaobing Krsnik, Zeljka Liu, Yuan Salamon, Iva Stephenson, Jessica D. Kraushar, Matthew L. Volk, Nicole L. Patel, Sejal M. Wijeratne, H. R. Sagara Li, Diana Suthar, Kandarp S. Wach, Aaron Sun, Miao Arnold, Sebastian J. Akamatsu, Wado Okano, Hideyuki Paillard, Luc Zhang, Huaye Buyske, Steven Kostovic, Ivica De Rubeis, Silvia Hart, Ronald P. Rasin, Mladen-Roko Nat Commun Article Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-seq analysis of mouse neocortical polysomes, here we report translationally repressed and derepressed mRNA isoforms during neocortical neurogenesis whose orthologs include risk genes for neurodevelopmental disorders. We demonstrate that the translation of distinct mRNA isoforms of the RNA binding protein (RBP), Elavl4, in radial glia progenitors and early neurons depends on its alternative 5′ UTRs. Furthermore, 5′ UTR-driven Elavl4 isoform-specific translation depends on upstream control by another RBP, Celf1. Celf1 regulation of Elavl4 translation dictates development of glutamatergic neurons. Our findings reveal a dynamic interplay between distinct RBPs and alternative 5′ UTRs in neuronal development and underscore the risk of post-transcriptional dysregulation in co-occurring neurodevelopmental disorders. Nature Publishing Group UK 2020-04-03 /pmc/articles/PMC7125149/ /pubmed/32245946 http://dx.doi.org/10.1038/s41467-020-15412-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Popovitchenko, Tatiana
Park, Yongkyu
Page, Nicholas F.
Luo, Xiaobing
Krsnik, Zeljka
Liu, Yuan
Salamon, Iva
Stephenson, Jessica D.
Kraushar, Matthew L.
Volk, Nicole L.
Patel, Sejal M.
Wijeratne, H. R. Sagara
Li, Diana
Suthar, Kandarp S.
Wach, Aaron
Sun, Miao
Arnold, Sebastian J.
Akamatsu, Wado
Okano, Hideyuki
Paillard, Luc
Zhang, Huaye
Buyske, Steven
Kostovic, Ivica
De Rubeis, Silvia
Hart, Ronald P.
Rasin, Mladen-Roko
Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title_full Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title_fullStr Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title_full_unstemmed Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title_short Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
title_sort translational derepression of elavl4 isoforms at their alternative 5′ utrs determines neuronal development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125149/
https://www.ncbi.nlm.nih.gov/pubmed/32245946
http://dx.doi.org/10.1038/s41467-020-15412-8
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