Intraspecies differences in transfer RNA (tRNA) methyltransferases have been investigated by comparing the activities of the liver tRNA-methylating enzymes of two inbred strains of mice. Since the tRNA methyltransferases are known to exhibit altered activities during carcinogenesis, it seemed of interest to compare the characteristics of these enzymes from inbred mice with either high (AKR/J) or low (C57BL/6J) incidence of spontaneous leukemia.

The activities of liver enzymes from AKR/J mice were found to be about 35% higher than those of the enzymes from mice of the C57BL/6J strain when assayed in vitro with heterologous mixed Escherichia coli tRNAs as substrate. When either E. coli tRNANfmet or tRNALeu2 was used as methyl group acceptor in the in vitro reaction, the activities of the enzymes from AKR/J mice were observed to be almost double those from the C57BL/6J animals. This contrasts with results obtained using E. coli tRNATyr as the methyl group acceptor, where no significant difference was observed between the methylase activity of enzymes from the livers of the two mouse strains. Under our assay conditions, E. coli tRNANfnet and tRNALeu2 are virtually base-specific substrates for the enzymatic transfer of methyl groups to guanine moieties in tRNA, while the products of tRNATyr methylation are 3 methylcytidine and 5 methylcytidine. The results of these experiments, using tRNA substrates of differing specificities, indicate that in these mice there are preferential differences in the guanine tRNA methyltransferases of liver. Enzymes from kidneys of AKR/J and C57BL/6J mice showed a similar 2-fold difference in activity with tRNANfmet as substrate.

The liver tRNA methyltransferase activity of F1 progeny of a cross between AKR and C57BL/6 showed intermediate levels of activity to those of the parental strains. This observation is consistent with additive inheritance. Further studies are under way to elucidate the mechanisms for genetic control of this enzyme system.

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This research was supported in part by NIH grants HL 09011 and CA 14906 and Department of Energy Contract EV10267.

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