<i>Caenorhabditis elegans</i> PRMT‑7 and PRMT‑9 Are Evolutionarily Conserved Protein Arginine Methyltransferases with Distinct Substrate Specificities

2017-04-25T00:00:00Z (GMT) by Andrea Hadjikyriacou Steven G. Clarke
<i>Caenorhabditis elegans</i> protein arginine methyltransferases PRMT-7 and PRMT-9 are two evolutionarily conserved enzymes, with distinct orthologs in plants, invertebrates, and vertebrates. Biochemical characterization of these two enzymes reveals that they share much in common with their mammalian orthologs. <i>C. elegans</i> PRMT-7 produces only monomethylarginine (MMA) and preferentially methylates R-X-R motifs in a broad collection of substrates, including human histone peptides and RG-rich peptides. In addition, the activity of the PRMT-7 enzyme is dependent on temperature, the presence of metal ions, and the reducing agent dithiothreitol. <i>C. elegans</i> PRMT-7 has a substrate specificity and a substrate preference different from those of mammalian PRMT7, and the available X-ray crystal structures of the PRMT7 orthologs show differences in active site architecture. <i>C. elegans</i> PRMT-9, on the other hand, produces symmetric dimethylarginine and MMA on SFTB-2, the conserved <i>C. elegans</i> ortholog of human RNA splicing factor SF3B2, indicating a possible role in the regulation of nematode splicing. In contrast to PRMT-7, <i>C. elegans</i> PRMT-9 appears to be biochemically indistinguishable from its human ortholog.