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

Popovitchenko, T., Park, Y., Page, N. F., Luo, X., Krsnik, Z., Liu, Y., et al. (2020). Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development. Nature Communications, 11(1): 1674. doi:10.1038/s41467-020-15412-8.

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NatCommun_Popovitchenko et al_2020.pdf (Publisher version), 7MB
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Popovitchenko, Tatiana , Author
Park, Yongkyu , Author
Page, Nicholas F. , Author
Luo, Xiaobing , Author
Krsnik, Zeljka , Author
Liu, Yuan , Author
Salamon, Iva , Author
Stephenson, Jessica D. , Author
Kraushar, Matthew1, 2, 3, Author           
Affiliations:
1High-Resolution Neurogenetics (Matthew Kraushar), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3374910              
2Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA, ou_persistent22              
3Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA, ou_persistent22              

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 Abstract: 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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Language(s): eng - English
 Dates: 2020-03-052020-04-03
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: DOI: 10.1038/s41467-020-15412-8
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 11 (1) Sequence Number: 1674 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723