It has been demonstrated that some tumor tRNA is undermethylated with respect to tRNA from normal tissues. Paradoxically, tumor cells contain higher activities of tRNA methyltransferases, the enzymes which methylate the tRNA. Certain tumor-derived tRNA methyltransferases are also capable of more exhaustive substrate tRNA methylation than are their counterparts from normal tissues, and at least one shows altered specificity. Studies will explore the cellular and molecular basis for the aberrant patterns of tRNA methylation seen in tumors. In order to facilitate our studies, we will generate hybridomas producing monoclonal antibodies against specific tRNA methyltransferases, the antibodies we will use to probe for structural differences between normal and tumor-derived enzymes. They will also be exploited for preparative purposes to yield quantities of enzymes sufficient for direct chemical analysis. At the cellular level, our aim is to determine the precise sites occupied by tRNA methylating enzyme by immunohistochemical methods. We will search for evidence of incorrect localization of these enzymes in tumor cells. Our investigations are intended to lead to a better understanding of the anomalies of RNA modification in neoplastic tissues. (H)
| Reinhart, M P; Lewis, J M; Leboy, P S (1986) A single tRNA (guanine)-methyltransferase from Tetrahymena with both mono- and di-methylating activity. Nucleic Acids Res 14:1131-48 |
