N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N-6-methyladenosine (m(6)A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m(6)A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m(6)A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m(6)A and positively regulates mRNA stability in an m(6)A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m(6)A 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 m(6)A, m(6)A interactors and mRNA homeostasis.