TY  - JOUR
AU  - Weise, Stefan C
AU  - Arumugam, Ganeshkumar
AU  - Villarreal, Alejandro
AU  - Videm, Pavankumar
AU  - Heidrich, Stefanie
AU  - Nebel, Nils
AU  - Dumit, Verónica I
AU  - Sananbenesi, Farahnaz
AU  - Reimann, Viktoria
AU  - Craske, Madeline
AU  - Schilling, Oliver
AU  - Hess, Wolfgang R
AU  - Fischer, Andre
AU  - Backofen, Rolf
AU  - Vogel, Tanja
TI  - FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus.
JO  - Molecular neurobiology
VL  - 56
IS  - 7
SN  - 0893-7648
CY  - Totowa, NJ
PB  - Humana Press
M1  - DZNE-2020-07244
SP  - 5188-5201
PY  - 2019
AB  - 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 Foxg1cre/+ 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.
KW  - Age Factors
KW  - Animals
KW  - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit: genetics
KW  - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit: metabolism
KW  - Forkhead Transcription Factors: genetics
KW  - Forkhead Transcription Factors: metabolism
KW  - Hippocampus: growth & development
KW  - Hippocampus: metabolism
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - MicroRNAs: genetics
KW  - MicroRNAs: metabolism
KW  - Nerve Tissue Proteins: genetics
KW  - Nerve Tissue Proteins: metabolism
KW  - Transcription, Genetic: physiology
KW  - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit (NLM Chemicals)
KW  - Forkhead Transcription Factors (NLM Chemicals)
KW  - Foxg1 protein, mouse (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
KW  - Mirn200 microRNA, mouse (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - PRKAR2B protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30539330
C2  - pmc:PMC6647430
DO  - DOI:10.1007/s12035-018-1444-7
UR  - https://pub.dzne.de/record/140922
ER  -