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Title[redir]:
FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA | Nature Communications
Description:
N6-methyladenosine is a prevalent internal modification in messenger RNA and non-coding RNA affecting various cellular pathways. Here we report the discovery of two additional modifications, N6-hydroxymethyladenosine (hm6A) and N6-formyladenosine (f6A), in mammalian messenger RNA. We show that FeII- and α-ketoglutarate-dependent fat mass and obesity-associated (FTO) protein oxidize N6-methyladenosine to generate N6-hydroxymethyladenosine as an intermediate modification, and N6-formyladenosine as a further oxidized product. N6-hydroxymethyladenosine and N6-formyladenosine have half-life times of ~3 h in aqueous solution under physiological relevant conditions, and are present in isolated messenger RNA from human cells as well as mouse tissues. These previously unknown modifications derived from the prevalent N6-methyladenosine in messenger RNA, formed through oxidative RNA demethylation, may dynamically modulate RNA–protein interactions to affect gene expression regulation. Internal modifications in mRNA and non-coding RNA are necessary for modulating various intracellular signalling pathways. In this study, the authors report novel modifications resulting from oxidative RNA demethylation, which regulate RNA–protein interactions affecting gene expression.
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Keywords {🔍}
hma, rna, fto, article, fig, supplementary, google, scholar, cas, oxidation, nature, modifications, mrna, reaction, protein, dna, demethylation, analysis, binding, mammalian, product, min, ads, human, base, mass, conditions, structure, cells, mouse, similar, coordinates, nmethyladenosine, cell, hmc, process, nuclease, methods, model, crystal, ftomediated, modification, alkb, observed, activity, figs, simulations, content, formation, methylation,
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nature portfolio permissions reprints haeme feii/α-kg-dependent dioxygenases privacy policy body mass index china scholarship council editing open biosystems advertising electron-rich nature glen research α-ketoglutarate-dependent fat mass pollution research full access high-resolution maldi-tof-ms 2′-o-t-butyldimethylsilyl adenosine 3′-o social media n-dimethylformamidine-protected tbdms-adenosine genome-wide-association studies development rnase-free solutions nature 485 nature 419 nature 187 nature 464 nature 468 nature quantitative lc-ms/ms haem feii/α-ketoglutarate alchemical free-energy simulations30 potential m6a-rna-binding protein4 ms/ms fragmentation pattern ke-li han modulate rna–protein interactions high-resolution mass spectra buffer solutions mimicking long-term exercise training weak acid n-hydroxybenzotriazole lc-qqq-ms/ms amidine-type protecting groups alchemical free-energy simulations dna epigenetic marker22 maldi-tof-ms analysis author correspondence active cofactor α-kg 9mer single-stranded rna ms/ms detection channel gst-tagged ythdf2 protein lc-ms/ms analysis maldi-tof ionization
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description:N6-methyladenosine is a prevalent internal modification in messenger RNA and non-coding RNA affecting various cellular pathways. Here we report the discovery of two additional modifications, N6-hydroxymethyladenosine (hm6A) and N6-formyladenosine (f6A), in mammalian messenger RNA. We show that FeII- and α-ketoglutarate-dependent fat mass and obesity-associated (FTO) protein oxidize N6-methyladenosine to generate N6-hydroxymethyladenosine as an intermediate modification, and N6-formyladenosine as a further oxidized product. N6-hydroxymethyladenosine and N6-formyladenosine have half-life times of ~3âh in aqueous solution under physiological relevant conditions, and are present in isolated messenger RNA from human cells as well as mouse tissues. These previously unknown modifications derived from the prevalent N6-methyladenosine in messenger RNA, formed through oxidative RNA demethylation, may dynamically modulate RNAâprotein interactions to affect gene expression regulation. Internal modifications in mRNA and non-coding RNA are necessary for modulating various intracellular signalling pathways. In this study, the authors report novel modifications resulting from oxidative RNA demethylation, which regulate RNAâprotein interactions affecting gene expression.
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