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Interferon-Induced and Double-Stranded RNA-Activated Proteins as Key Enzymes Regulating Protein Synthesis

  • Chapter
Translational Regulation of Gene Expression 2

Abstract

In 1971, Hunt and Ehrenfeld1,2 demonstrated for the first time the inhibition of protein synthesis in rabbit reticulocytes by double-stranded RNA (dsRNA) extracted from poliovirus-infected HeLa cells. This inhibition was confirmed by a wide variety of synthetic and naturally occurring dsRNAs.3 During this time, Ian Kerr and collaborates4–6 demonstrated a similar type of inhibition of protein synthesis by dsRNA in cell-free systems prepared from interferon-treated cells. In addition to this, they showed that when cell-free systems were prepared from interferon-treated and virus-infected cells, protein synthesis was inhibited. Thus, the requirement for dsRNA was abolished by virus infection. This was due to the production of viral dsRNA-like molecules during the infection. These observations pointed out two requirements for the inhibition of protein synthesis in cell-free systems: first, interferon treatment of cells, and second, addition of dsRNA in the cell-free system. Accordingly, the initial objectives were then to specify the components that were induced by interferon and which interacted with dsRNA. Eventually, it became clear that an enzyme responsible for the synthesis of a low-molecular-weight oligonucleotide inhibitor (later referred to as 2-5A) and a protein kinase were likely to be involved.7–14

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Hovanessian, A.G. (1993). Interferon-Induced and Double-Stranded RNA-Activated Proteins as Key Enzymes Regulating Protein Synthesis. In: Ilan, J. (eds) Translational Regulation of Gene Expression 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2894-4_8

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