Abstract
Queuosine (Q), found exclusively in th first position of the anticodons of tRNAAsp, tRNAAsn, tRNAHis and tRNATyr, is synthesized in eucaryotes by a base-for-base exchange of queuine, the base of Q, for guanine at tRNA position 34. This reaction is catalyzed by the enzyme tRNA-guaning transglucosylate (EC 2.4.2.29). We measured the specific release of queuine from Q-5′-phsphate (queuine salvage) and the extent of tRNA Q modification in 6 human tumors carried as xenografts in immune-deprived mice. Q-deficient tRNA was found in 3 of the tumors but it did not correlate with diminished queuine salvage. The low tRNA Q content of one tumor, the HxGC3 colo adenocarcinoma, prompted us to examine a HxGC3-derived cell line, GC3/M. GC3/M completely lacks Q in its tRNA and measurable tRNA-guanine transglycosylase activity; the first example of a higher eucaryotic cell which lacks this enzyme. Exposure of GC3/M cells to 5-azacytidine induces the transient appearance of Q-positive tRNA. This result suggests that at least one allele of the transglycosylase gene in GC3/M cells may have been inactivated by DNA methylation. In clinical samples, we found Q-deficient tRNA in 10 of 46 solid tumors, including 2 of 13 colonic carcinomas.
Original language | English (US) |
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Pages (from-to) | 229-238 |
Number of pages | 10 |
Journal | BBA - Molecular Basis of Disease |
Volume | 1139 |
Issue number | 3 |
DOIs | |
State | Published - Jul 7 1992 |
Externally published | Yes |
Keywords
- 5-Axazytidine
- DNA methylation
- Human tumor
- Queuine
- Queuosine
- tRNA-guanine transglycosylase
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology