Oligonucleotide inhibitor of proteii of interferon-treated chick embryo with the mouse low molecular weig (mechanism of interferon action/double-stranded RNA/avian ce

Cytoplasmic extracts of interferon-treated primary chick embryo cells contain an enzyme activity that synthesized an inhibitor of chick cell-free protein synthesis. The same activity was detected in extracts of cells treated with mock preparations of interferon, but at <0.3% of the level found in interferon-treated cell extracts. The enzyme was activated by double-stranded RNA and could be isolated by binding to col- umns of poly(I).poly(C)agarose. In the column-bound state, the enzyme reacted with ATP to synthesize the inhibitor, which could then be continuously eluted from the column. The in- hibitor was purified and its structure and function were com- pared with those of the low molecular weight inhibitor of pro- tein synthesis made by an enzyme from interferon-treated mouse L cells. The avian and mammalian inhibitors comigrated on thin layers of polyethyleneimine-cellulose during chroma- tography in three different solvent systems, and they coeluted as a series of peaks from columns of DEAE-cellulose during sodium chloride gradient elution. Digestion with bacterial al- kaline phosphatase or snake venom phosphodiesterase yielded products that similarly comigrated. Functionally, the two in- hibitors were interchangeable: both inhibited protein synthesis in extracts of mammalian and avian cells, producing 50% in- hibition at a concentration of about 0.3 nM (AMP equivalents). We conclude that the chick cell-derived oligonucleotide inhib- itor has a structure that is closely related or identical to that of the inhibitor made in the mouse system, and that both prepa- rations inhibit cell-free protein synthesis in a non-species-spe- cific manner.