FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA
Ye Fu,
Guifang Jia,
Xueqin Pang,
Richard N. Wang,
Xiao Wang,
Charles J. Li,
Scott Smemo,
Qing Dai,
Kathleen A. Bailey,
Marcelo A. Nobrega,
Ke-Li Han,
Qiang Cui and
Chuan He ()
Additional contact information
Ye Fu: The University of Chicago
Guifang Jia: The University of Chicago
Xueqin Pang: University of Wisconsin
Richard N. Wang: The University of Chicago
Xiao Wang: The University of Chicago
Charles J. Li: The University of Chicago
Scott Smemo: The University of Chicago
Qing Dai: The University of Chicago
Kathleen A. Bailey: The University of Chicago
Marcelo A. Nobrega: The University of Chicago
Ke-Li Han: State Key Laboratory of Molecular Reaction Dynamics and Center for Theoretical and Computational Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Qiang Cui: University of Wisconsin
Chuan He: The University of Chicago
Nature Communications, 2013, vol. 4, issue 1, 1-8
Abstract:
Abstract 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.
Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2822
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DOI: 10.1038/ncomms2822
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