Paul L. Boutz Department of Biochemistry and Biophysics, Center for RNA Biology, Center for Biomedical Informatics, Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York 14620, USA Corresponding author: paul_boutzurmc.rochester.edu Abstract

Specialized enzymes add methyl groups to the nitrogens of the amino acid histidine, altering the chemical properties of its imidazole ring and, in turn, the function of the modified (poly)peptide. In this issue of Genes & Development, Shimazu and colleagues (pp. 724–742) make the remarkable discovery that CARNMT1 acts as a dual-specificity histidine methyltransferase, modifying both the small-molecule dipeptide carnosine and a set of proteins, predominantly within RNA-binding C3H zinc finger (C3H ZF) motifs. As a result, CARNMT1 modulates the activity of its protein targets to affect RNA processing and metabolism, ultimately contributing an essential function during mammalian development.