Proteomics

Dataset Information

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Identification of FOXG1 interaction partners


ABSTRACT: Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent non-congenital form called atypical Rett syndrome. FOXG1 is a key transcription factor implicated in forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using SILAC based quantitative proteomics and genome-wide small RNA sequencing, we identified that FOXG1 interacts with the ATP-dependent RNA helicase, DDX5/p68 and controls the biogenesis of miRNAs. Both, FOXG1 and DDX5 bind to the miR200b/a/429 primary transcript and associate with the microprocessor complex, whereby DDX5 recruits FOXG1 to DROSHA. In vivo and in vitro experiments show that both FOXG1 and DDX5 are necessary for effective maturation of miR200b/a/429. RNAseq analyses of Foxg1-heterozygote hippocampi and miR200b/a/429 overexpressing Neuro-2a cells revealed that the cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) is a target of miR200 in neural cells. Since it is known that PRKAR2B inhibits postsynaptic functions by attenuating protein kinase A (PKA) activity, increased PRKAR2B levels may contribute to neuronal dysfunctions in FOXG1 Rett syndrome.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Rett Syndrome

SUBMITTER: Veronica Dumit  

LAB HEAD: Veronica Dumit

PROVIDER: PXD007040 | Pride | 2019-11-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20160709_JuDo_CFP_985_1_1.RAW Raw
20160709_JuDo_CFP_985_1_10.RAW Raw
20160709_JuDo_CFP_985_1_2.RAW Raw
20160709_JuDo_CFP_985_1_3.RAW Raw
20160709_JuDo_CFP_985_1_4.RAW Raw
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Publications


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/4  ...[more]

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