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

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...

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Autores principales: Filippini, Alice, Bonini, Daniela, Lacoux, Caroline, Pacini, Laura, Zingariello, Maria, Sancillo, Laura, Bosisio, Daniela, Salvi, Valentina, Mingardi, Jessica, La Via, Luca, Zalfa, Francesca, Bagni, Claudia, Barbon, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785225/
https://www.ncbi.nlm.nih.gov/pubmed/28640668
http://dx.doi.org/10.1080/15476286.2017.1338232
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author Filippini, Alice
Bonini, Daniela
Lacoux, Caroline
Pacini, Laura
Zingariello, Maria
Sancillo, Laura
Bosisio, Daniela
Salvi, Valentina
Mingardi, Jessica
La Via, Luca
Zalfa, Francesca
Bagni, Claudia
Barbon, Alessandro
author_facet Filippini, Alice
Bonini, Daniela
Lacoux, Caroline
Pacini, Laura
Zingariello, Maria
Sancillo, Laura
Bosisio, Daniela
Salvi, Valentina
Mingardi, Jessica
La Via, Luca
Zalfa, Francesca
Bagni, Claudia
Barbon, Alessandro
author_sort Filippini, Alice
collection PubMed
description 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.
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spelling pubmed-57852252018-01-30 Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse Filippini, Alice Bonini, Daniela Lacoux, Caroline Pacini, Laura Zingariello, Maria Sancillo, Laura Bosisio, Daniela Salvi, Valentina Mingardi, Jessica La Via, Luca Zalfa, Francesca Bagni, Claudia Barbon, Alessandro RNA Biol Research Paper 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. Taylor & Francis 2017-09-05 /pmc/articles/PMC5785225/ /pubmed/28640668 http://dx.doi.org/10.1080/15476286.2017.1338232 Text en © 2017 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Filippini, Alice
Bonini, Daniela
Lacoux, Caroline
Pacini, Laura
Zingariello, Maria
Sancillo, Laura
Bosisio, Daniela
Salvi, Valentina
Mingardi, Jessica
La Via, Luca
Zalfa, Francesca
Bagni, Claudia
Barbon, Alessandro
Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title_full Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title_fullStr Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title_full_unstemmed Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title_short Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
title_sort absence of the fragile x mental retardation protein results in defects of rna editing of neuronal mrnas in mouse
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785225/
https://www.ncbi.nlm.nih.gov/pubmed/28640668
http://dx.doi.org/10.1080/15476286.2017.1338232
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