Molecular Pharmacology, Vol 2, 43-49, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

The Selective Inhibition of Ribosomal RNA Synthesis in E. coli by 2,4-Dinitrophenol

¹ Department of Medicine, New York University School of Medicine, New York, New York, and The Summer Research Institute, Will Rogers Hospital and O’Donnell Memorial Laboratories, Saranac Lake, New York

2,4-Dinitrophenol (DNP), when added to cultures of Escherichia coli in concentrations not greatly in excess of those required to inhibit growth, exhibits marked inhibition of RNA synthesis, while little effect on DNA and protein synthesis is seen. The selectivity disappears rapidly with increasing concentrations of DNP. Evidence is presented which demonstrates that low concentrations of DNP inhibit primarily the synthesis of ribosomal RNA with relatively slight effects on the synthesis of messenger and transfer RNA’s. At the concentrations at which selectivity is observed, neither oxidative phosphorylation nor transport of uracil across the cell membrane appears to be affected appreciably by DNP. The similarities and differences between the modes of action of levorphanol and of DNP are discussed.

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ACKNOWLEDGMENTS This work was supported by grant MH-10227 from the National Institutes of Health and from grant U-1006 from the Health Research Council of the City of New York. The authors are grateful to Dr. R. Hausmann for his assistance with the bacteriophage experiments and to Drs. I. Smith and J. Hurwitz for performing the methylation assays on the "starved" sRNA. The authors wish to thank Miss Sandra Peltz and Miss Susan Travis, who performed a number of the experiments as fellows at The Summer Research Institute of the Will Rogers Hospital.