Control of Synthesis and Wastage of Ribosomal Ribonucleic Acid in Lymphocytes

Resting lymphocytes were found to accumulate rRNA in their cytoplasm at only half the rate at which the molecules were synthesized in the nucleus. This discrepancy was reversed by stimulating cell growth. This confirms, by independent means, conclusions reached previously on the basis of evidence showing rapid degradation of a large portion of newly synthesized 18 S rRNA in resting lymphocytes. By pulse chase studies with l-[methyl-3H]methionine it was shown that degradation of a fraction of newly synthesized 18 S rRNA molecules occurs shortly after cleavage of the 45 S pre-rRNA into 32 S and 18 S segments. Survival of new 18 S rRNA molecules was found to be dependent on continuous synthesis of a protein or proteins. Reduction of protein synthesis with cycloheximide caused exaggeration of 18 S RNA wastage normally occurring in resting cells. Increasing protein synthesis by temperature elevation reduced 18 S RNA wastage. Partial reduction of rRNA synthesis by low doses of actinomycin D caused an increased survival of those 18 S RNA molecules synthesized. This suggests that the protective protein acts on the new 18 S RNA molecule to prevent attack by ribonucleases, rather than acting on the degradative enzymes to alter their activity. The data support the conclusion that the survival of new 18 S rRNA molecules in resting lymphocytes is controlled by the rate of synthesis of a continuously produced protein. This control may act as a regulator of cell growth.