Special RepoRt Bioinformatic identification of novel methyltransferases

Methyltransferases & epigenomics In recent years, we have witnessed greatly expanded attention to the enzymes that catalyze the transfer of methyl groups from S-adenosylmethionine (AdoMet) to DNA, RNA, proteins, lipids and small molecules [1]. The central role of methyltransferases in epigenetics was first realized with enzymes modifying DNA [2,3]; subsequent work has demonstrated the importance of a number of enzymes that modify lysine and arginine residues in histones [4–7]. RNA methyltransferases also appear to play a role. For example, microRNA species can be modified by methyltransferases such as HEN1 to affect DNA methylation in paramutation [8–11]. It is likely that additional methyltransferases for protein, RNA, DNA and perhaps even lipids or small molecules, may be involved in epigenetic phenomena. For the human proteome, only a fraction of the potential methyltransferases has been functionally identified and enzymes of importance to epigenetics may be lurking among the unknown species. Thus, it is of interest to be able to identify the complete ‘cast’ of methyltransferases and their substrates in the proteomes of various organisms. In this paper, we review recent progress on the identification and characterization of new methyltransferases. We have focused our discussion largely on the situation in the budding yeast Saccharomyces cerevisiae, where the ‘methyl transferasome’ has been most fully characterized [12,13] (Table 1). The successful identification of yeast methyltransferases will hopefully help pave the way to the identification of new enzymes in higher plants, mammals and other organisms. We will first introduce the different methyltransferase families and what bioinformatic methods have helped reveal about them, along with the limitations of these methods. We will then describe one biochemical approach to determining the function of candidate methyl transferases identified using bioinformatics methods.