Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 03, 2020
- Source ID
- 10.1038/s41467-020-15412-8
Entities
People
- Aaron Wach
- Diana Li
- H. R. Sagara Wijeratne
- Hideyuki Okano
- Huaye Zhang
- Iva Salamon
- Ivica Kostovic
- Jessica D Stephenson
- Kandarp S Suthar
- Luc Paillard
- Matthew L Kraushar
- Miao Sun
- Mladen-roko Rasin
- Nicholas F Page
- Nicole L. Volk
- Ronald P. Hart
- Sebastian J Arnold
- Sejal M. Patel
- Silvia De Rubeis
- Steven Buyske
- Tatiana Popovitchenko
- Wado Akamatsu
- Xiaobing Luo
- Yongkyu Park
- Yuan Liu
- Željka Krsnik
Organizations
- Beatrice and Samuel A. Seaver Foundation
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense
- United States Department of Health and Human Services