Weise, Stefan C.Stefan C.WeiseArumugam, GaneshkumarGaneshkumarArumugamVillarreal, AlejandroAlejandroVillarrealVidem, PavankumarPavankumarVidemHeidrich, StefanieStefanieHeidrichNebel, NilsNilsNebelDumit, Verónica I.Verónica I.DumitSananbenesi, FarahnazFarahnazSananbenesiReimann, ViktoriaViktoriaReimannCraske, MadelineMadelineCraskeSchilling, OliverOliverSchillingHess, Wolfgang R.Wolfgang R.HessFischer, AndréAndréFischerBackofen, RolfRolfBackofenVogel, TanjaTanjaVogel2019-07-092019-07-092018https://resolver.sub.uni-goettingen.de/purl?gro-2/59877Rett 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.enCC BY 4.0https://creativecommons.org/licenses/by/4.0610journal_article10.1007/s12035-018-1444-730539330https://resolver.sub.uni-goettingen.de/purl?gs-1/16050