Ribonucleic Acid-Dependent Ribonucleic Acid Replicase in the Immune Response

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An immune ribonucleic acid (iRNA) preparation was made using phenol extracts of spleens of mice previously immunized with Salmonella tennessee flagella. An enzyme, also prepared from the spleens of these mice, induced the incorporation of 3H-UTP into the acid-insoluble fraction in a cell-free system in the presence of this RNA. The enzyme activity could be demonstrated from the spleens of immunized mice but not from normal ones, and this activity was also inhibited by two derivatives of rifamycin. Treatment with ribonuclease or heating at alkaline pH resulted in a loss of activity in added RNA. The 3H-uridine-labeled product was found resistant to ribo-nuclease treatment but became sensitive when the product was subjected to heat treatment. However, actinomycin D, mitomycin C or bleomycin A2 did not inactivate the enzyme activity. These results suggest that this enzyme induces the incorporation of UTP into the acid-insoluble fraction using iRNA as a template and the product may be a newly synthesized RNA which forms a hybrid with iRNA. This enzyme activity may play a role in the antibody formation process, and may account for the in vivo replication of iRNA by this enzyme, viz., probably an RNA-dependent RNA replicase.

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