RNA methyltransferases involved in 5' cap biosynthesis

Byszewska, Magdalena; Smietanski, Miroslaw; Purta, Elzbieta; Bujnicki, Janusz M

The Abd1 protein from Saccharomyces cerevisiae is a monofunctional cap0 methyltransferase, and biochemically has been one of the best studied methyltransferases involved in cap structure biosynthesis. 2, 22, 23 Its enzymatic activity is critical for yeast cell growth and the gene ABD1 that encodes the Abd1 protein is essential. Abd1 is a founding member of a protein family that is strongly conserved in eukaryotes as well as in viruses. 24 The crystal structure of S. cerevisiae Abd1 itself could not be determined, but eventually it was solved for its homolog, the Ecm1 protein from E. cuniculi (Fig. 2) . 25 Purified Ecm1 is a monomeric protein that catalyzes methyl transfer to GpppRNA to form cap0, but also to free mononucleotides GTP, GDP or dGTP (deoxy-GTP). The methyltransferase domain in Ecm1, and by inference also in other homologous cap0 methyltransferases, exhibits the RFM fold with a characteristic insertion that forms a characteristic b-meander structure involved in the formation of the capbinding site. This insertion is common between methyltransferases that methylate G to m 7 G in the RNA cap, and methyltransferases that N-methylate the amino acid glycine. This relationship between 2 different types of methyltransferases, as well as the cap0 methyltransferase structure, were correctly predicted using bioinformatics 24 before the first structure of the cap0 methyltransferase was determined.