[Mechanisms of the regulation of the biological activity of the cell by 2',5-oligoadenylate]. / Mekhanizmy reguliatsii biologicheskoi aktivnosti kletki s uchastiem 2',5'-oligoadenilata.

The problems of regulation of biological activity of the cell, in particular, of such complicated processes as cell growth, differentiation, etc., rank highest among the most burning problems of present-day biology. A great majority of regulatory systems have been discovered, which control the biological activity of the cell. Among those, a most multifunctional and thoroughly investigated one is the cAMP system. The mechanisms of cAMP-dependent regulation, cAMP-dependent enzymes and other aspects of the system function have become the subject of numerous experimental papers, reviews and monographs. Another regulatory system which presently attracts the wide attention of investigators is the 2',5'-oligoadenylate system. The aim of the present review is to summarize the current data on the action mechanism and biological significance of 2',5'-oligoadenylate. Besides, the authors analyze some experimental results concerning the mechanisms of interaction and mutual regulation of the two above-mentioned systems.

On the fidelity of DNA replication: use of synthetic oligonucleotide-initiated reactions.

The phi X174 fidelity system provides a biological assay for quantitating the accuracy of DNA polymerases. Expansion of this system to cell extracts and DNA replication complexes from eucaryotes has been limited by the presence of nucleases in these preparations. We have overcome these limitations by priming the phi X template with a synthetic oligodeoxynucleotide, with its free 3'-hydroxyl terminus only a short distance from the amber locus that is the site for determining the frequency of misincorporation. In this paper, this modified phi X system is characterized and compared to that using defined natural DNA restriction fragments as primers. The modified system has been applied to studies on the fidelity of DNA synthesis using different forms of purified DNA polymerase-alpha from calf thymus, as well as crude extracts from human lymphocytes.

Effect of oligonucleotide AGAGGAGGU on protein synthesis in vitro.

The oligonucleotide AGAGGAGGU, complementary to the 3' end of 16S RNA has been shown to inhibit 70S initiation complex formation on E. coli ribosomes (Taniguchi, T. and Weissmann, C., 1978. Nature, 275, 770-772). We have prepared this nonanucleotide in larger quantities by a combination of DEAE cellulose-urea chromatography and reverse phase (RPC 5) chromatography. The inhibitory effect of AGAGGAGGU on initiation complex formation has been confirmed. Furthermore, when added to a complete system for in vitro protein synthesis, the translation of Q beta RNA was inhibited by the nonanucleotide. No selectivity was observed in the inhibition of the coat protein and replicase protein synthesis. When both Q beta RNA and pAUG were present, some stimulation of pAUG binding to 70S ribosomes was observed on addition of AGAGGAGGU, as previously reported (Taniguchi and Weissmann, ibid). No effect was observed in the absence of Q beta RNA. This observation is discussed.

Natural occurrence of 2-5A in interferon-treated EMC virus-infected L cells.

Until now the interferon-mediated 2'-5' adenine oligonucleotide inhibitors (2-5A) of cell-free protein synthesis have not been detected in intact cells. Here we report their natural occurrence in interferon-treated, EMC virus-infected mouse L cells in amounts consistent with the idea that they play a part in the inhibition of virus growth.

Anorexia-producing intermediary metabolites.

Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells.

[Oligonucleotides of human thrombocytes and their participation in the release reaction induced by thrombin]. / Oligonukleotidy trombotsitov cheloveka i ikh uchastie v reaktsii vysvobozhdeniia, indutsirovannoi trombinom

The presence of a fraction of oligonucleotides rich in adenin, and a high metabolic activity of this fraction was demonstrated. Data are presented on the participation of adenin-rich oligonucleotides of human platelets in the blood coagulation system reactions, namely in the release reaction induced by thrombin.