Modulating Transfer RNA Anticodon Modifications and Biologic Responses in Human Cells

摘要

This research project was designed to assess the role of tRNA anticodon modifications in regulating gene expression and to determine the potential for manipulating these modifications to modulate biologic responses in human cells. The modification reactions of primary interest were those involved in generating the nucleosides queuosine and inosine exclusively in the first position of the anticodon of specific tRNAs. These are the only two tRNA modifications known to occur by base exchange mechanisms, whereby queuine and hypoxanthine are inserted directly into tRNA macromolecules. Various human cell culture systems were used to determine whether and/or how the dietary factor queuine and the normal purine catabolite hypoxanthine: Inhibit the effects of tumor promoters, block the neoplastic process subsequent to the initiation event, reverse the expression of transformed phenotypes by malignant cells, and induce the maturation of undifferentiated cells. The relationship to specific tRNA structural changes in the anticodon was evaluated.