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

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 Neural Stem Cells / metabolism Neurogenesis / genetics Neuroglia / metabolism Neurons / metabolism Polyribosomes / metabolism Primary Cell Culture Protein Biosynthesis / genetics RNA Isoforms / genetics RNA-Seq

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
03 04 2020
Historique:
received: 04 10 2018
accepted: 05 03 2020
entrez: 5 4 2020
pubmed: 5 4 2020
medline: 1 8 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-15412-8 PMID: 32245946 PMC: PMC7125149
pubmed: 32245946
doi: 10.1038/s41467-020-15412-8
pii: 10.1038/s41467-020-15412-8
pmc: PMC7125149
doi:

Substances chimiques

5' Untranslated Regions 0
CELF1 Protein 0
CELF1 protein, mouse 0
ELAV-Like Protein 4 0
Elavl4 protein, mouse 0
RNA Isoforms 0
Glutamic Acid 3KX376GY7L

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1674

Subventions

Organisme : NINDS NIH HHS
ID : R00 NS064303
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS075367
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089578
Pays : United States
Organisme : NIMH NIH HHS
ID : F30 MH106220
Pays : United States

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Auteurs

Tatiana Popovitchenko (T)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA.
ORCID: 0000-0002-6600-4667

Yongkyu Park (Y)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
ORCID: 0000-0001-6741-6447

Nicholas F Page (NF)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA.
ORCID: 0000-0001-7173-5408

Xiaobing Luo (X)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Zeljka Krsnik (Z)

Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia.
ORCID: 0000-0001-5238-6820

Yuan Liu (Y)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA.

Iva Salamon (I)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA.
Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia.
ORCID: 0000-0003-3817-1983

Jessica D Stephenson (JD)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
ORCID: 0000-0001-9807-8436

Matthew L Kraushar (ML)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
Graduate Program in Neurosciences, Rutgers University, Piscataway, NJ, 08854, USA.
ORCID: 0000-0002-7359-0318

Nicole L Volk (NL)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Sejal M Patel (SM)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

H R Sagara Wijeratne (HRS)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Diana Li (D)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Kandarp S Suthar (KS)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
ORCID: 0000-0001-8739-728X

Aaron Wach (A)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
ORCID: 0000-0003-0963-2779

Miao Sun (M)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Sebastian J Arnold (SJ)

Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, D-79104, Germany.
ORCID: 0000-0002-2688-9210

Wado Akamatsu (W)

Department of Physiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.

Hideyuki Okano (H)

Department of Physiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.

Luc Paillard (L)

Univ Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes)-UMR 6290, F-35000, Rennes, France.

Huaye Zhang (H)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.

Steven Buyske (S)

Department of Statistics, Rutgers University, Piscataway, NJ, 08854, USA.
ORCID: 0000-0001-8539-5416

Ivica Kostovic (I)

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 (S)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA.
Seaver Autism Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Ronald P Hart (RP)

Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA.
ORCID: 0000-0003-4836-8712

Mladen-Roko Rasin (MR)

Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA. roko.rasin@rutgers.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Régions non traduites › Régions 5' non traduites › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Épissage alternatif › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Eucaryotes › Animaux › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Protéines à motif de reconnaissance de l'ARN › Protéines CELF › Protéine CELF1 › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Protéines à motif de reconnaissance de l'ARN › Antigènes Hu de l'encéphalomyélite paranéoplasique › Protéine-4 similaire à ELAV › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes au cours du développement › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés excitateurs › Acide glutamique › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Néocortex › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches neurales › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neurogenèse › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Cellules › Névroglie › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Cellules › Neurones › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Ribosomes › Polyribosomes › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Biosynthèse des protéines › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Isoformes d'ARN › Translational derepression of Elavl4 isoforms...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Translational derepression of Elavl4 isoforms...