Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_3F5DA390795D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse.
Périodique
RNA biology
Auteur⸱e⸱s
Filippini A., Bonini D., Lacoux C., Pacini L., Zingariello M., Sancillo L., Bosisio D., Salvi V., Mingardi J., La Via L., Zalfa F., Bagni C., Barbon A.
ISSN
1555-8584 (Electronic)
ISSN-L
1547-6286
Statut éditorial
Publié
Date de publication
02/11/2017
Peer-reviewed
Oui
Volume
14
Numéro
11
Pages
1580-1591
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. To evaluate the ADAR2-FMRP interaction in mammals we analyzed several RNA editing re-coding sites in the fmr1 knockout (KO) mice. Ex vivo and in vitro analysis revealed that absence of FMRP leads to an increase in the editing levels of brain specific mRNAs, indicating that FMRP might act as an inhibitor of editing activity. Proximity Ligation Assay (PLA) in mouse primary cortical neurons and in non-neuronal cells revealed that ADAR2 and FMRP co-localize in the nucleus. The ADAR2-FMRP co-localization was further observed by double-immunogold Electron Microscopy (EM) in the hippocampus. Moreover, ADAR2-FMRP interaction appeared to be RNA independent. Because changes in the editing pattern are associated with neuropsychiatric and neurodevelopmental disorders, we propose that the increased editing observed in the fmr1-KO mice might contribute to the FXS molecular phenotypes.
Mots-clé
Adenosine Deaminase/genetics, Adenosine Deaminase/metabolism, Animals, Cell Nucleus/metabolism, Cell Nucleus/ultrastructure, Cerebral Cortex/metabolism, Cerebral Cortex/pathology, Disease Models, Animal, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, Fragile X Syndrome/pathology, Gene Deletion, Hippocampus/metabolism, Hippocampus/pathology, Humans, Male, Mice, Mice, Knockout, Neurons/metabolism, Neurons/pathology, Phenotype, Primary Cell Culture, Protein Binding, RNA Editing, RNA, Messenger/genetics, RNA, Messenger/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, ADAR2, FMRP, Fragile X syndrome, RNA editing
Pubmed
Web of science
Création de la notice
06/07/2017 17:34
Dernière modification de la notice
20/08/2019 13:36
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