protein in order to catalyze tRNA modification. However, unlike the interaction of seryl-tRNA synthetase with Trm140p, which allows Trm140p to recognize and modify different seryl-tRNA isoacceptors in S. cerevisiae, the tRNA-binding specificity of DALRD3 limits METTL2A/B activity to only tRNA-Arg-UCU and CCU. The need to discriminate between the different arginine tRNA isoacceptors could explain why mammals evolved DALRD3 to interact with METTL2 rather than arginyl-tRNA synthetase. Another possibility is that METTL2 contributes primarily to substrate specificity while DALRD3 serves as an activator of METTL2 methyltransferase activity.
