Molecular Biology

Unmethylating RNA

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Science  04 Nov 2011:
Vol. 334, Issue 6056, pp. 569-571
DOI: 10.1126/science.334.6056.569-d

There is much excitement about the role of the Tet enzymes in the active demethylation of eukaryotic DNA, especially as DNA methyaltion plays such a central role in gene regulation and genome stability. The role of methylation in eukaryotic RNA is more enigmatic: Here, the dominant modification is the conversion of adenosine (A) to N6-methyadenosine (m6A).

The fat mass–and–obesity–associated (FTO) gene is involved in energy homeostasis, and variants in the human FTO gene are correlated with body mass. FTO has been associated with a number of enzymatic activities, including demethylation of the methylated bases m3T and m3U in single-stranded (ss) DNA and ssRNA. In vitro, Jia et al. now show that whereas FTO can indeed demethylate m3U, it is much more effective at converting m6A to A in RNA oligomers, including the sequence of a known m6A modifi cation site. FTO had a similar effect in vivo, reducing or increasing the level of m6A in whole-cell RNA when overexpressed or knocked down, respectively. In the nucleus, FTO associated specifi cally with speckles that contain RNA splicing factors and RNA polymerase II. Although its knockdown does not seem to affect assembly of the spliceosome, the authors suggest that FTO might yet be part of a regulatory system with parallels to DNA and histone methylation

Nat. Chem. Biol. 7, 10.1038/NCHEMBIO.687 (2011).

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