Nucleic Acids Research, 1981, Vol. 9, No. 19 4939-4950
© 1981
ENZYMOLOGY |
Structural requirements of polynucleotides for the activation of (2'-5')An polymerase and protein kinase
1Department of Biological Sciences, State University of New York at Albany Albany, NY 12222, USA 2Rega Institute for Medical Research, Katholieke Universiteit Leuven B-3000 Leuven, Belgium
Received July 14, 1981.
Two enzymatic pathways are involved in the inhibitory effects of double-stranded (ds)RNA on protein synthesis in cell extracts derived from interferon-treated human fibroblasts or HeLa cells, an oligonucleotide polymerase that synthesizes (2'-5')An from ATP and a protein kinase that phosphorylates the 
subunit of initiation factor eIF-2 as well as a polypeptide of Mr = 72,000. We have now evaluated the activation of both the (2'-5')An polymerase and protein kinase by a large variety of polynucleotides, including natural and synthetic dsRNAs, homopolymers, alternating copolymers, triple-stranded polymers, purine-purine duplexes and purine-pyrimidine duplexes with modifications at either the pyrimidine or ribose moieties. All these polynucleotides have been the subject of previous interferon induction studies. Some polynucleotides, i.e. (I)n.(C)n and mycophage dsRNA, which have been recognized as excellent interferon inducers, were also potent activators of both (2'-5')An polymerase and protein kinase, whereas non-inducers such as (A)n.(X)n and (A)n.(br5u)n did not activate either the kinase or the polymerase. However, some polymers like (I)n.(br5C)n, (dIfl)n.(C)n and (dIcl)n.(C)n, while potent interferon inducers and kinase activators, behaved poorly as activators of the (2'-5')An polymerase. Other polymers, i.e. (dAfl)n.(U)n and (A)n.(U)n. (I)n, that do not induce interferon, activated the kinase but not the polymerase. Finally, (I)n.(s2c)n, a relatively potent interferon inducer, did not activate either kinase or polymerase. These findings indicate that there is no simple relationship between the interferon-inducing ability of dsRNAs and their stimulating effects on (2'-5')An polymerase and protein kinase activity.
+Friedrich Miescher Institut, CH-4002 Basel, Switzerland
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