J. Biol. Chem., Vol. 258, Issue 4, 2118-2121, 02, 1983
Increase in S-adenosylhomocysteine concentration in interferon-treated HeLa cells and inhibition of methylation of vesicular stomatitis virus mRNA
F de Ferra and C Baglioni
A fraction of the viral mRNA synthesized in interferon-treated HeLa cells
infected with vesicular stomatitis virus (VSV) lacks the 7-methyl group in
the 5'-terminal guanosine of the cap; this mRNA is not associated with
polyribosomes and does not bind to ribosomes in an assay for initiation of
protein synthesis (de Ferra, F., and Baglioni, C. (1981) Virology 112,
426-435). To establish whether this defect in methylation is due to changes
in the level of the methyl donor S- adenosylmethionine (AdoMet) and of its
competitive inhibitor S- adenosylhomocysteine (AdoHcy), we measured the
concentration of these compounds in HeLa cells treated with interferon. An
increase in both AdoMet and AdoHcy was detected 3 to 6 h after addition of
interferon. The level of these compounds increased gradually and in
proportion to the interferon concentration used. With 125 reference
units/ml of beta interferon, for example, the AdoHcy concentration
increased more than 3- fold and that of AdoMet about 1.5-fold with a
consequent change in the AdoHcy/AdoMet ratio. An increased AdoHcy/AdoMet
ratio was also found in HeLa cells treated with pure alpha 2 interferon
produced in Escherichia coli by recombinant DNA techniques. When the
methylation of VSV mRNA was measured in assays carried out with
permeabilized virions at the AdoHcy and AdoMet concentrations found in
interferon-treated cells, a preferential inhibition of the viral
(guanine-7-)methyltransferase activity was observed. Such an inhibition may
account for the synthesis of VSV mRNA lacking the 7-methyl group of
guanosine in the cap.
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