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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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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. |
format | Online Article Text |
id | pubmed-5785225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
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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