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

Tatiana Popovitchenko; Yongkyu Park; Nicholas F Page; Xiaobing Luo; Zeljka Krsnik; Yuan Liu; Iva Salamon; Jessica D Stephenson; Matthew L Kraushar; Nicole L Volk; Sejal M Patel; H R Sagara Wijeratne; Diana Li; Kandarp S Suthar; Aaron Wach; Miao Sun; Sebastian J Arnold; Wado Akamatsu; Hideyuki Okano; Luc Paillard; Huaye Zhang; Steven Buyske; Ivica Kostovic; Silvia De Rubeis; Ronald P Hart; Mladen-Roko Rasin

doi:10.1038/s41467-020-15412-8

Back

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

Journal article

Open access

Peer reviewed

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

Tatiana Popovitchenko, Yongkyu Park, Nicholas F Page, Xiaobing Luo, Zeljka Krsnik, Yuan Liu, Iva Salamon, Jessica D Stephenson, Matthew L Kraushar, Nicole L Volk, …

Nature communications, Vol.11(1), pp.1674-1674

04/03/2020

DOI: https://doi.org/10.1038/s41467-020-15412-8

PMCID: PMC7125149

PMID: 32245946

Abstract

5' Untranslated Regions - genetics

Alternative Splicing

Animals

CELF1 Protein - metabolism

Cell Line, Tumor

ELAV-Like Protein 4 - genetics

Female

Gene Expression Regulation, Developmental

Glutamic Acid - metabolism

Male

Mice

Mice, Transgenic

Neocortex - cytology

Neocortex - growth & development

Neural Stem Cells - metabolism

Neurogenesis - genetics

Neuroglia - metabolism

Neurons - metabolism

Polyribosomes - metabolism

Primary Cell Culture

Protein Biosynthesis - genetics

RNA Isoforms - genetics

RNA-Seq

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.

Files and links (1)

url

https://doi.org/10.1038/s41467-020-15412-8View

Version of Record (VoR) Open

Metrics

20 Record Views

31 Times Cited - Web of Science

See more details

Details

Title: Translational derepression of Elavl4 isoforms at their alternative 5' UTRs determines neuronal development
Creators: Tatiana Popovitchenko - Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA
Yongkyu Park - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Nicholas F Page - Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA
Xiaobing Luo - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Zeljka Krsnik - Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia
Yuan Liu - Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA
Iva Salamon - Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia
Jessica D Stephenson - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Matthew L Kraushar - Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA
Nicole L Volk - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Sejal M Patel - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
H R Sagara Wijeratne - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Diana Li - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Kandarp S Suthar - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Aaron Wach - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Miao Sun - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Sebastian J Arnold - Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, D-79104, Germany
Wado Akamatsu - Department of Physiology, Keio University School of Medicine, Tokyo, 160-8582, Japan
Hideyuki Okano - Department of Physiology, Keio University School of Medicine, Tokyo, 160-8582, Japan
Luc Paillard - Univ Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes)-UMR 6290, F-35000, Rennes, France
Huaye Zhang - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
Steven Buyske - Department of Statistics, Rutgers University, Piscataway, NJ, 08854, USA
Ivica Kostovic - Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia
Silvia De Rubeis - Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Ronald P Hart - Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA
Mladen-Roko Rasin - Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA. roko.rasin@rutgers.edu
Publication Details: Nature communications, Vol.11(1), pp.1674-1674
Date published: 04/03/2020
Grant note: R01 NS075367 / NINDS NIH HHS R00 NS064303 / NINDS NIH HHS F30 MH106220 / NIMH NIH HHS
Academic Unit: Neuroscience and Cell Biology (RWJMS); Statistics (SAS); Honors College at Rutgers - New Brunswick; W.M. Keck Center of Collaborative Neuroscience
Language: English
Resource Type: Journal article
Identifiers: 991031665975504646