Peptidylarginine methyltransferases (PRMTs) methylate arginine residues in polypeptides, increasing the structural and functional diversity of proteins involved in the regulation of numerous cellular processes, including histones. PRMT1 is the major PRMT in mammalian cells, responsible for more than 85% of all protein arginine methylation; yet surprisingly little is known about its own regulation. On p. 638, Yannis Robin-Lespinasse and colleagues report that human CCR4-associated factor 1 (hCAF1) regulates PRMT1 activity. They demonstrate that hCAF1 and PRMT1 directly interact in vivo and co-localise to the same sub-nuclear compartment. Furthermore, hCAF1 acts as a cofactor for PRMT1 and regulates its enzymatic activity in vitro in a substrate-specific manner. Loss-of-function studies show that hCAF1 modulates asymmetric methylation of endogenous PRMT1 substrates in vivo. Indeed, methylation of the nuclear RNA-binding protein Sam68 and histone H4, two PRMT1-specific substrates, increased following hCAF1 ablation. The authors thus identify hCAF1 as a novel regulator of PRMT1 function. They go on to speculate that regulation of methyltransferase activity by hCAF1 may contribute to the crosstalk between transcription and RNA processing.