Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras.
basic_science · Level V
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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-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.
Medical subject headings
- Adenine Nucleotides
- NF-kappa B
- Oligonucleotides, Antisense
- Oligoribonucleotides
- Protein Serine-Threonine Kinases
- Signal Transduction