Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse
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| Název: | Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse |
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| Autoři: | Alice Filippini, Valentina Salvi, Jessica Mingardi, Luca La Via, Laura Sancillo, Claudia Bagni, Caroline Lacoux, Francesca Zalfa, Daniela Bosisio, Maria Zingariello, Laura Pacini, Daniela Bonini, Alessandro Barbon |
| Přispěvatelé: | ProdInra, Migration, Università degli Studi di Brescia = University of Brescia (UniBs), Department of Biomedicine and Prevention, Università degli Studi di Roma Tor Vergata Roma, Italia = University of Rome Tor Vergata Rome, Italy = Université de Rome Tor Vergata Rome, Italie, Università Campus Bio-Medico di Roma, Partenaires INRAE, Università degli studi 'G. d'Annunzio' Chieti-Pescara Chieti-Pescara (Ud'A), Flanders Institute for Biotechnology, Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV), MIUR (PRIN) 2012A9T2S9_004, Fondazione Cariplo, Associazione Italiana Sindrome X Fragile, Telethon GGP15257, Lejeune Foundation, 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 |
| Zdroj: | RNA Biol RNA biology, vol. 14, no. 11, pp. 1580-1591 |
| Informace o vydavateli: | Informa UK Limited, 2017. |
| Rok vydání: | 2017 |
| Témata: | Male, 0301 basic medicine, RNA editing, Adenosine Deaminase, Knockout, [SDV]Life Sciences [q-bio], Messenger, 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, 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, Molecular Biology, Cell Biology, RNA-Binding Protein, Hippocampus, Fragile X Mental Retardation Protein, 03 medical and health sciences, Hippocampu, Settore BIO/13 - BIOLOGIA APPLICATA, RNA, Messenger, Cell Nucleu, RNA editing, FMRP, Cell Nucleus, Cerebral Cortex, Neurons, 0303 health sciences, Animal, RNA-Binding Proteins, Neuron, [SDV] Life Sciences [q-bio], Fragile X Syndrome, Disease Models, RNA, Human, Research Paper |
| Popis: | 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. |
| Druh dokumentu: | Article Other literature type Conference object |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1555-8584 1547-6286 |
| DOI: | 10.1080/15476286.2017.1338232 |
| DOI: | 10.6084/m9.figshare.5139259.v1 |
| DOI: | 10.6084/m9.figshare.5139259 |
| Přístupová URL adresa: | https://www.tandfonline.com/doi/pdf/10.1080/15476286.2017.1338232?needAccess=true https://pubmed.ncbi.nlm.nih.gov/28640668 https://pubmed.ncbi.nlm.nih.gov/28640668/ https://serval.unil.ch/resource/serval:BIB_3F5DA390795D.P001/REF.pdf https://core.ac.uk/display/149488223 http://europepmc.org/articles/PMC5785225 https://www.tandfonline.com/doi/full/10.1080/15476286.2017.1338232 https://www.tandfonline.com/doi/pdf/10.1080/15476286.2017.1338232 http://www.tandfonline.com/toc/krnb20/current https://doi.org/10.1080/15476286.2017.1338232 https://hdl.handle.net/11564/675464 https://hdl.handle.net/10281/383992 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_3F5DA390795D7 https://serval.unil.ch/notice/serval:BIB_3F5DA390795D https://serval.unil.ch/resource/serval:BIB_3F5DA390795D.P001/REF.pdf https://hdl.handle.net/11379/513375 |
| Rights: | CC BY NC ND CC BY |
| Přístupové číslo: | edsair.doi.dedup.....2c40c3e79b9fdb4f78e85c082a4eb63e |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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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| ISSN: | 15558584 15476286 |
| DOI: | 10.1080/15476286.2017.1338232 |