FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA.

Abstract:

:N(6)-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, N(6)-hydroxymethyladenosine (hm(6)A) and N(6)-formyladenosine (f(6)A), in mammalian messenger RNA. We show that Fe(II)- and α-ketoglutarate-dependent fat mass and obesity-associated (FTO) protein oxidize N(6)-methyladenosine to generate N(6)-hydroxymethyladenosine as an intermediate modification, and N(6)-formyladenosine as a further oxidized product. N(6)-hydroxymethyladenosine and N(6)-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 N(6)-methyladenosine in messenger RNA, formed through oxidative RNA demethylation, may dynamically modulate RNA-protein interactions to affect gene expression regulation.

journal_name

Nat Commun

journal_title

Nature communications

authors

Fu Y,Jia G,Pang X,Wang RN,Wang X,Li CJ,Smemo S,Dai Q,Bailey KA,Nobrega MA,Han KL,Cui Q,He C

doi

10.1038/ncomms2822

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

1798

issn

2041-1723

pii

ncomms2822

journal_volume

4

pub_type

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