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

Avudaiappan Maran, Ratan K. Maitra, Aseem Kumar, Beihua Dong, Wei Xiao, Guiying Li, Bryan R.G. Williams, Paul F. Torrence, Robert H. Silverman

Research output: Contribution to journalArticleResearchpeer-review

208 Citations (Scopus)

Abstract

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-κB (NF-κB) by the dsRNA poly(I):poly(C), which provides direct evidence that PKR is a transducer for the dsRNA signaling of NF-κB.

Original languageEnglish
Pages (from-to)789-792
Number of pages4
JournalScience
Volume265
Issue number5173
DOIs
Publication statusPublished - 5 Aug 1994
Externally publishedYes

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