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FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus
Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent form of atypical Rett syndrome, called FOXG1 syndrome. FOXG1 is a key transcription factor crucial for forebrain development, where it maintains the b...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647430/ https://www.ncbi.nlm.nih.gov/pubmed/30539330 http://dx.doi.org/10.1007/s12035-018-1444-7 |
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author | Weise, Stefan C. Arumugam, Ganeshkumar Villarreal, Alejandro Videm, Pavankumar Heidrich, Stefanie Nebel, Nils Dumit, Verónica I. Sananbenesi, Farahnaz Reimann, Viktoria Craske, Madeline Schilling, Oliver Hess, Wolfgang R. Fischer, Andre Backofen, Rolf Vogel, Tanja |
author_facet | Weise, Stefan C. Arumugam, Ganeshkumar Villarreal, Alejandro Videm, Pavankumar Heidrich, Stefanie Nebel, Nils Dumit, Verónica I. Sananbenesi, Farahnaz Reimann, Viktoria Craske, Madeline Schilling, Oliver Hess, Wolfgang R. Fischer, Andre Backofen, Rolf Vogel, Tanja |
author_sort | Weise, Stefan C. |
collection | PubMed |
description | Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent form of atypical Rett syndrome, called FOXG1 syndrome. FOXG1 is a key transcription factor crucial for forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using genome-wide small RNA sequencing and quantitative proteomics, we identified that FOXG1 affects the biogenesis of miR200b/a/429 and interacts with the ATP-dependent RNA helicase, DDX5/p68. Both FOXG1 and DDX5 associate with the microprocessor complex, whereby DDX5 recruits FOXG1 to DROSHA. RNA-Seq analyses of Foxg1(cre/+) hippocampi and N2a cells overexpressing miR200 family members identified cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) as a target of miR200 in neural cells. PRKAR2B inhibits postsynaptic functions by attenuating protein kinase A (PKA) activity; thus, increased PRKAR2B levels may contribute to neuronal dysfunctions in FOXG1 syndrome. Our data suggest that FOXG1 regulates PRKAR2B expression both on transcriptional and posttranscriptional levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1444-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6647430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-66474302019-08-06 FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus Weise, Stefan C. Arumugam, Ganeshkumar Villarreal, Alejandro Videm, Pavankumar Heidrich, Stefanie Nebel, Nils Dumit, Verónica I. Sananbenesi, Farahnaz Reimann, Viktoria Craske, Madeline Schilling, Oliver Hess, Wolfgang R. Fischer, Andre Backofen, Rolf Vogel, Tanja Mol Neurobiol Article Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent form of atypical Rett syndrome, called FOXG1 syndrome. FOXG1 is a key transcription factor crucial for forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using genome-wide small RNA sequencing and quantitative proteomics, we identified that FOXG1 affects the biogenesis of miR200b/a/429 and interacts with the ATP-dependent RNA helicase, DDX5/p68. Both FOXG1 and DDX5 associate with the microprocessor complex, whereby DDX5 recruits FOXG1 to DROSHA. RNA-Seq analyses of Foxg1(cre/+) hippocampi and N2a cells overexpressing miR200 family members identified cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) as a target of miR200 in neural cells. PRKAR2B inhibits postsynaptic functions by attenuating protein kinase A (PKA) activity; thus, increased PRKAR2B levels may contribute to neuronal dysfunctions in FOXG1 syndrome. Our data suggest that FOXG1 regulates PRKAR2B expression both on transcriptional and posttranscriptional levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1444-7) contains supplementary material, which is available to authorized users. Springer US 2018-12-11 2019 /pmc/articles/PMC6647430/ /pubmed/30539330 http://dx.doi.org/10.1007/s12035-018-1444-7 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Weise, Stefan C. Arumugam, Ganeshkumar Villarreal, Alejandro Videm, Pavankumar Heidrich, Stefanie Nebel, Nils Dumit, Verónica I. Sananbenesi, Farahnaz Reimann, Viktoria Craske, Madeline Schilling, Oliver Hess, Wolfgang R. Fischer, Andre Backofen, Rolf Vogel, Tanja FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title | FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title_full | FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title_fullStr | FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title_full_unstemmed | FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title_short | FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus |
title_sort | foxg1 regulates prkar2b transcriptionally and posttranscriptionally via mir200 in the adult hippocampus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647430/ https://www.ncbi.nlm.nih.gov/pubmed/30539330 http://dx.doi.org/10.1007/s12035-018-1444-7 |
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