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FTO Dynamics in Synaptic Toxicity

ABSTRACT: FTO (Fat Mass and Obesity-associated protein), acts as an RNA m6A demethylase. It targets and removes methyl groups from N6-methyladenosine (m6A) residues in RNA, facilitating a reversible modification that plays a pivotal role in RNA metabolism. FTO shows selective and sparse localization within synapses, hinting at its specialized role in synaptic modulation. Experimentally induced transitions in FTO expression, from endogenous states to targeted overexpression and shifts from nuclear to pan-neuronal and synaptic localizations, reveal its complex regulatory functions and the effects on the m6A regulatory machinery. Notably, NMDA receptor activation and kinase activity are critical in redistributing FTO to synapses. The synaptic concentration of FTO directly impacts synaptic plasticity and integrity. Moreover, the downregulation of FTO highlights the complex role of FTO in cognitive functions. Our findings provide insights into the potential therapeutic strategies for enhancing cognitive resilience and addressing synaptic pathologies associated with altered FTO dynamics.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE263395 | GEO | 2025/12/01

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE263395_diffPeaks_control_AAV_FTO_exomePeak2_output.csv.gz	Csv
	GSE263395_diffPeaks_control_radicicol_exomePeak2_output.csv.gz	Csv
	GSE263395_diffPeaks_control_sindbis_FTO_exomePeak2_output.csv.gz	Csv
	GSE263395_protein_coding_genes_raw_counts.txt.gz	Txt

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The Obesity-associated Fto gene regulates activity of the dopaminergic midbrain circuitry [FTO KO]

Project description:Here we use MeRIP-Seq to analyze global adenosine methylation (m6A) in mRNAs in the midbrain and striatum of Fto-deficient mice. We find that Fto deficiency leads to increased methylation within a subset of mRNAs important for neuronal signaling, including many within the dopaminergic signaling pathway. Collectively, our results show that Fto regulates demethylation of specific mRNAs in vivo, and this activity relates to control of dopaminergic transmission. Profiling of m6A in midbrain and striatum from FTO knockout mice

2013-06-15 | E-GEOD-47216 | biostudies-arrayexpress

Quantitative Proteomics of Mouse Liver (FTO-KO,WT) in response to DEN injection

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VHL acts as an adaptor to promote the phosphorylation of FTO by CK2 to suppress clear cell renal cell carcinoma

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