Structural requirements of (2′–5′) oligoadenylate for protein synthesis inhibition in human fibroblasts
- 1 January 1982
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 10 (6) , 2163-2174
- https://doi.org/10.1093/nar/10.6.2163
Abstract
The structural requirements of (2'-5')-oligoadenylic acid (pppA(2'p5'A)x, X greater than or equal to 1 or (2'-5'An) for inhibition of protein synthesis in cells were examined with a modified calcium-coprecipitation technique, using a series of trinucleotide analogs (pppA2'p5'A2'p5'N, N=rC, rG, rU, T, dC, dG, dA). In this system both the degree and the duration of the inhibition of protein synthesis were dependent on the added concentration of (2'-5')A3. Of all the heterotrimers, only the deoxy A derivative was active as an inhibitor of protein synthesis, while the other members of the analog series were found to have no inhibitory effects. In competition experiments between (2'-5')A3 and the non-active analogs, three heterotrimers were shown to reduce the activity of (2'-5')A3 in protein inhibition. In contrast, the dephosphorylated (2'-5')A3 had no inhibitory effect and was not effective in blocking (2'-5')A3. These results indicate that the 5'-terminal triphosphate is important for binding of (2'-5')A3 to the site of (2'-5')An action and the adenine base at the 2'-terminus is important for activating the machinery responsible for protein synthesis inhibition in the cells, most likely the (2'-5')An-activated nuclease.Keywords
This publication has 33 references indexed in Scilit:
- Interferon Action: RNA Cleavage Pattern of a (2′-5′)Oligoadenylate—Dependent EndonucleaseScience, 1981
- The 2′5′ oligoadenylate synthetase has a multifunctional 2′5′ nucleotidyl-transferase activityBiochemical and Biophysical Research Communications, 1981
- Synthesis and characterization of (2′-5′)ppp3′dA(p3′dA)n, an analogue of (2′-5′)pppA(pA)nNature, 1981
- Species-specific posttranscriptional regulation of interferon synthesisBiochemistry, 1980
- Activation of a nuclease by pppA2′p5′ A2′p5′ A in intact cellsFEBS Letters, 1979
- Interferon-induced enzymatic activities and their role in the antiviral stateCell, 1979
- Enzymic Synthesis, Characterisation and Nuclear‐Magnetic‐Resonance Spectra of pppA2′p5′A2′p5′A and Related Oligonucleotides: Comparison with Chemically Synthesised MaterialEuropean Journal of Biochemistry, 1979
- Interferon action: Isolation of Nuclease F, A translation inhibitor activated by interferon‐induced (2′–5′) oligo‐isoadenylateFEBS Letters, 1978
- Interferon, double-stranded RNA and RNA degradation. Fractionation of the endonucleaseINT system into two macromolecular components; Role of a small molecule in nuclease activationBiochemical and Biophysical Research Communications, 1978
- Interferon, Double‐Stranded RNA and RNA DegradationEuropean Journal of Biochemistry, 1977