Interferon action: Isolation of Nuclease F, A translation inhibitor activated by interferon-induced (2′–5′) oligo-isoadenylate (original) (raw)
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Proceedings of the National Academy of Sciences, 1979
A phosphodiesterase characterized by a generally higher activity on 2'-5' than on 3'-5' phosphodiester bonds was isolated from mouse L cells treated with interferon. A similar enzyme was purified from mouse reticulocytes. The phosphodiesterase 2'-PDi splits the 2'-phosphate bond of pppA2'p5'A2'p5'A, the oligonucleotide activator of ribonuclease F. The level of phosphodiesterase 2'-PDi is increased by interferon treatment of L cells. The phosphodiesterase was also shown to degrade the C-C-A terminus of tRNA and to reduce the amino acid acceptance of tRNA in cell-free extracts, thereby causing a tRNA-reversible inhibition of mRNA translation. In extracts of interferon-treated cells, translation of mRNA into proteins is inhibited by several enzymatic pathways (1-3). One pathway is mediated by the double-stranded RNA (dsRNA)/ ATP-activated protein kinase PK-i, induced by interferon in the cells (1, 3), which phosphorylates eukaryotic initiation factor 2 and decreases Met-tRNAf et binding to 40S ribosomes (4). A
Proceedings of the National Academy of Sciences, 1978
101. Assay of an Interferon-induced enzyme in white blood cells as a diagnostic aid in viral diseases. A. Schattner , D. Wallach, G. Merlin, T. Hahn, S. Levin and M. Revel. The Lancet 2, 497-500, 1981. 110. Preferential effect of interferon-γ on the synthesis of HLA antigens and their mRNAs in human cells. D. Wallach, M. Fellous and M. Revel. Nature 299, 833-836, 1982. 129. Effective constitutive production of human fibroblast IFN-β by hamster cells transformed with the IFN-β1. gene fused to an SV40 early promoter.
Molecular and Cellular Biochemistry, 1983
The effects of double-stranded RNA (dsRNA) on interferon (IFN)-induced antiviral and anticellular activities was investigated by introducing poly(I)-poly(C) into mouse L-cells. Coprecipitation ofdsRNA with calcium phosphate enabled its efficient penetration into cells in culture. Rate of cellular protein synthesis was inhibited by dsRNA only in cultures pretreated with IFN. Moreover, the anticellular effect of IFN, as measured by the inhibition of cell DNA synthesis, was also enhanced by dsRNA. The kinetics of dsRNA-mediated inhibition of protein synthesis were relatively slow as compared with the inhibitory effect of 2'-5'oligoadenylic acid (2'5'A), which was also introduced into cells by the calcium phosphate coprecipitation technique. To analyze the effects of dsRNA on the antiviral state induced by IFN, vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMC), replications were followed by measuring viral-specific RNA synthesis in the cell. Introduction of dsRNA after the infection had no effect on VSV and EMC replication in control cells, and it enhanced, to a small extent, the antiviral state of cells pretreated with IFN. In contrast, introduction of 2'5'A into virus-infected cells inhibited VSV and EMC replications regardless of IFN pretreatment. This work demonstrated that the role of dsRNA in regulating the antiviral and anticellular activities of IFN could be studied by introducing exogenous dsRNA into cells in culture by the calcium phosphate coprecipitation technique. Abbreviations 2'5'A = triphosphoadenyl (2'5') adenylyl (2'-5') adenosine; Pi = the interferon-induced 67 000 dalton protein; RNase F = the 2'5'A-dependent ribonuclease; Hepes = 4-(2-hydroxy)-l-piperazineethane sulfonic acid.
Double-Stranded Rna and the Enzymology of Interferon Action
Annals of the New York Academy of Sciences, 1980
Interferons were discovered in 1957 as antiviral agents.' Investigations in the last 22 years, however, revealed their involvement in the regulation of a large variety of seemingly diverse physiological phenomena and processes. These include for example cell growth, delayed hypersensitivity, graft rejection, histocompatibility antigen expression, natural killer-cell recruitment and macrophage activation. It appears to be in line with this multiplicity of effects that the biochemistry of interferon (IF) action is also complex. Much of our knowledge of this biochemistry is based on the comparison of enzyme activities in extracts from IF-treated and control cells and has been gained in the last five In this communication we will summarize briefly our studies of two enzyme systems controlled by IF. The action of one results in the accelerated cleavage of single-stranded RNA, that of the other in the impairment of peptide chain initiation. The two enzyme systems are distinct, though both require doublestranded (ds) RNA for activation' (see also references 4 and 6-9). Our studies concerning other effects of IF treatment of cells on enzyme reactions ( e g . an impairment of mRNA cap methylation in vitro and in vivoto-'' and the acceleration of tRNA inactivation in vitroI3) have been summarized e 1 s e~h e r e . l~
69-kDa and 100-kDa isoforms of interferon-induced (2'-5') oligoadenylate …
European Journal of …, 1997
The (2'-5')oligoadenylate synthetase represents a family of interferon-induced proteins which when activated by double-stranded (ds)RNA polymerizes ATP into 2'-5'-linked oligomers with the general formula pppA(2'p5'A) n , where n > 1, which for convenience are referred to ...
Double-stranded RNA inhibits a phosphoprotein phosphatase present in interferon-treated cells
Proceedings of the National Academy of Sciences, 1980
In accord with previous studies, (I)n . (C)n, a potent inhibitor of the cell-free protein-synthesizing system of interferon-treated L cells, stimulates incorporation of 32P from [gamma-32P]ATP into the 67,000-dalton protein, P1. The double-stranded RNA (I)n . (br5C)n, which is inactive as an inhibitory of protein synthesis, does not stimulate phosphorylation of P1 under conditions approximating those of protein synthesis. However, we have found conditions under which (I)n . (br5C)n is approximately as effective as (I)n . (C)n in stimulating incorporation of label from [gamma-32P]ATP into 67,000-dalton protein. Upon transfer of labeled P1 from these conditions to those compatible with protein synthesis, there is a time-dependent decrease in label in the 67,000-dalton protein. This decrease is more rapid in the presence of (I)n . (br5C)n than in the presence of (I)n . (C)n. This differential decrease is also observed when 32P-labeled extracts are diluted into buffer containing 10 mM A...