Defective transfer RNA-queuine modification in C3H10T1/2 murine fibroblasts transfected with oncogenic ras.
tRNA isoacceptors for aspartic acid, asparagine, histidine, and tyrosine are modified in the anticodon wobble position with the deazaguanine analogue queuine. Queuine modification is defective in many tumors and transformed cell lines, and the extent of hypomodification correlates with staging and outcome in numerous human tumors. The molecular role of queuine modification in normal cells and the mechanisms of queuine hypomodification in tumors are unknown. We have characterized nontransformed C3H10T1/2 murine fibroblasts (C3H) and their ras-transfected counterparts (RasC4) with respect to the causes and effects of queuine hypomodification. RasC4 cells are hypomodified for queuine compared with C3H cells, despite increase tRNA-guanine ribosyltansferase activity. Excess exogenous queuine can cause repletion of tRNA queuine levels in RasC4 cells. Queuine modification of both C3H and RasC4 cells can be decreased by treatment with 7-methylguanine. This treatment does not affect growth in monolayer culture but enhances anchorage-independent growth of RasC4 cells greatly. These cell lines may be useful systems for the study of queuine function in normal cells and the causes and consequences of hypomodification for queuine in tumors.
Morgan
C J
CJ
Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Merrill
F L
FL
Trewyn
R W
RW
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011905:Genes, ras; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010430:Pentosyltransferases / Q000378:metabolism; D010641:Phenotype; D012343:RNA, Transfer / Q000187:drug effects* / Q000378:metabolism*; D014162:Transfection
D006147:Guanine; C019549:queuine; D012343:RNA, Transfer; D010430:Pentosyltransferases; C020837:queuine tRNA-ribosyltransferase