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Studies Dealing with Hepatic RNA Metabolism in Rats Force-Fed a Threonine-Devoid Diet^1,2,

Department of Pathology, The George Washington University Medical Center, Washington, DC 20037

Young rats were force-fed for 3 days a purified diet devoid of threonine and a number of aspects relating to RNA metabolism in the livers were studied. The findings in the livers of rats force-fed the threonine-devoid diet in comparison with those force-fed the complete diet were as follows: a) poly(A)-mRNA was increased in nuclei and in polyribosomes; b) DNA-dependent RNA polymerases I and II activities were increased; c) in vitro release of ¹⁴C-orotic acid labeled RNA from nuclei revealed that transport was unchanged and nucleoside triphosphatase activity of nuclear envelopes was unchanged; d) polyribosomes (total, free and membrane-bound) shifted toward heavier aggregation and in vitro ¹⁴C-leucine incorporation into protein was increased; e) RNase activities (at pH 5.4, 7.6 or 9.5) were essentially unaltered; and f) in vivo ¹⁴C-choline incorporation into microsomal membranes was increased. By administering selected inhibitors of RNA and protein synthesis, such as actinomycin D, -amanitin or cycloheximide, prior to killing the rats force-fed the threonine-devoid or complete diet for 3 days, it was demonstrated that the stimulatory effect on hepatic polyribosomes and protein synthesis in the experimental group was dependent upon new synthesis of poly(A)mRNA and of protein.

KEY WORDS: • threonine deficiency • RNA metabolism • protein synthesis

¹ Supported by U.S. Public Health Service Research Grant AM 21079 from the National Institute of Arthritis, Metabolism and Digestive Diseases.

² A preliminary report was presented at the Meeting of the Federation of American Societies for Experimental Biology in Atlantic City, NJ, April 1978; Fed. Proc. 37, 751 (abs.).

Manuscript received 12 May 1980.