Mechanism of 5-azacytidine-induced transfer RNA cytosine-5-methyltransferase deficiency

Leejane Lu, K. Randerath

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The administration of 5-azacytidine to mice leads to a specific, rapid, time-dependent, and dose-dependent decrease of transfer RNA (tRNA) cytosine-5-methyltransferase activity of mouse liver and the synthesis of tRNA specifically lacking 5-methylcytidine. The mechanism of this enzyme deficiency was investigated. The pretreatment of mice with RNA synthesis inhibitors such as actinomycin D and D-galactosamine prevented the enzyme deficiency induced by 5-azacytidine administration. These results suggested that RNA synthesis was a prerequisite for the induction by 5-azacytidine of the enzyme inhibition in vivo. Indeed, a slowly sedimenting RNA (4 to 7S) from the livers of mice treated with 5-azacytidine, when present in an in vitro tRNA methyltransferase assay, decreased specifically the activity of tRNA cytosine-5-methyltransferase. The pretreatment of mice with actinomycin D or D-glactosamine prior to the administration of 5-azacytidine effectively prevented the formation of such inhibitory RNA in vivo as determined by an in vitro tRNA methyltransferase assay. These results indicate that the administration of 5-azacytidine to mice leads to the rapid synthesis of a low-molecular-weight RNA fraction which is capable of specifically inactivating tRNA cytosine-5-methyltransferase activity in vivo and in vitro.

Original languageEnglish (US)
JournalCancer Research
Volume40
Issue number8
StatePublished - 1980
Externally publishedYes

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Azacitidine
Transfer RNA
tRNA Methyltransferases
RNA
Dactinomycin
Enzymes
Nucleic Acid Synthesis Inhibitors
Galactosamine
Liver
Cytosine 5-methyltransferase
Molecular Weight
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mechanism of 5-azacytidine-induced transfer RNA cytosine-5-methyltransferase deficiency. / Lu, Leejane; Randerath, K.

In: Cancer Research, Vol. 40, No. 8, 1980.

Research output: Contribution to journalArticle

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