Absence of tRNA-guanine transglycosylase in a human colon adenocarcinoma cell line

Ufuk Gündüz, Mark S. Elliott, Patricia H. Seubert, Janet A. Houghton, Peter J. Houghton, Ronald W. Trewyn, Jon R. Katze

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalBBA - Molecular Basis of Disease
Volume1139
Issue number3
DOIs
StatePublished - Jul 7 1992
Externally publishedYes

Keywords

  • 5-Axazytidine
  • DNA methylation
  • Human tumor
  • Queuine
  • Queuosine
  • tRNA-guanine transglycosylase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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