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- Title
Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development.
- Authors
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
- 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. Translational regulation of isoforms in the developing nervous system is not well understood. Here, the authors report translational de-repression of RNA binding protein isoforms at their 5′UTRs in the neocortex and show the neurodevelopmental risk of post-transcriptional dysregulation.
- Subjects
RNA-binding proteins; GENETIC regulation; NERVOUS system; NEUROGLIA; NEURAL development; NEURON development; RNA splicing
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-15412-8