N-methyladenosine (mA) recruits and repels proteins to regulate mRNA homeostasis.

RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N-methyladenosine (mA), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to mA to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of mA interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by mA and positively regulates mRNA stability in an mA-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent mA reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among mA, mA interactors and mRNA homeostasis.