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A moonlighting function: the methionine cycle rewires RNA methylation

Zhaoxu Xu^1,2,3 , Jianjun Chen^1,2,3,*

¹Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA
²Center for RNA Biology and Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA
³Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
* Correspondence: Jianjun Chen(jianchen@coh.org)

Methionine metabolism is classically viewed as an epigenetic supply line that fuels the methylation of histones, DNA, and RNA via the universal methyl donor S-adenosylmethionine (SAM). In a recent Cell Research study, Liao et al. uncover a SAM-independent mechanism in which the methionine-cycle enzyme adenosylhomocysteinase (AHCY) moonlights as a metabolite-gated scaffold, rewiring mRNA N6-methyladenosine (m6A) regulation by tuning the activity of the RNA demethylase FTO.

https://doi.org/10.1038/s41422-026-01231-x

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