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Science 5 August 1994:
Vol. 265. no. 5173, pp. 789 - 792
DOI: 10.1126/science.7914032
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Articles

Science, Vol 265, Issue 5173, 789-792
Copyright © 1994 by American Association for the Advancement of Science

articles

Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras

A Maran, RK Maitra, A Kumar, B Dong, W Xiao, G Li, BR Williams, PF Torrence, and RH Silverman

Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.

Activation of 2-5A-dependent ribonuclease by 5'-phosphorylated, 2',5'-linked oligoadenylates, known as 2-5A, is one pathway of interferon action. Unaided uptake into HeLa cells of 2-5A linked to an antisense oligonucleotide resulted in the selective ablation of messenger RNA for the double-stranded RNA (dsRNA)-dependent protein kinase PKR. Similarly, purified, recombinant human 2-5A-dependent ribonuclease was induced to selectively cleave PKR messenger RNA. Cells depleted of PKR activity were unresponsive to activation of nuclear factor-kappa B (NF-kappa B) by the dsRNA poly(I):poly(C), which provides direct evidence that PKR is a transducer for the dsRNA signaling of NF-kappa B.


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