GENETIC COMPLEMENTATION OF RADIATION RESPONSE BY 3'-UNTRANSLATED REGIONS (UTR) OF RNA

The molecular basis of radiosensitivity was studied using a cDNA compl ementation approach to correct radiosensitivity in cells. Four cDNAs o f sizes 1.6, 2.0, 2.2 and 2.5 kb were isolated that corrected several aspects of the phenotype of cells from patients with the human genetic disorder ataxia-telangiectasia, characterized by hypersensitivity to ionizing radiation. The criteria used to assess correction included ce ll viability, induced chromosome aberrations, G(2) phase delay and ind uction of p53 after exposure to radiation. One cDNA (2.5 kb) was ident ified as the complete sequence of the RNA helicase p68, which was capa ble of correcting radiosensitivity based on two of the above four crit eria, with p53 induction post irradiation being partially corrected. T he 2.2 kb cDNA was shown to correspond to the complete sequence of arg inyl tRNA synthetase and the other two cDNAs were identical to the 3' untranslated regions (UTR) of the transcription factor TFIIS (1.6 kb) and phospholipase A2 (2.0 kb) respectively. Additional transfections w ith the 3'UTR (198 nucleotides) of p68 RNA helicase and its inverse se quence revealed that the 3'UTR had the same complementation capacity a s the full-length cDNA, whereas the inverse construct failed to comple ment radiosensitivity. These data provide additional support for a nov el role for 3'UTRs in the regulation of gene expression.