Ribosomal Ribonucleic Acid Production and Growth Regulation in Human Lymphocytes

Much evidence indicates that ribosomal RNA in animal cells is first synthesized as a 45 S precursor which is cleaved to form a 32 S molecule and a molecule of 18 S rRNA. The 32 S molecule is subsequently converted to 28 S rRNA. From this model it follows that the two classes of rRNA should be produced in equimolar amounts. When newly synthesized RNA in growing human lymphocytes was labeled with Urd-3H, the ratio of radioactive 18 S:32-28 S rRNA was consistent with equimolar production of the two rRNA classes, as expected. However, nongrowing lymphocytes showed an apparent deficiency of new 18 S rRNA relative to the amount of 32-28 S rRNA produced. The deficiency was found to be the result of temporary retention in the nucleus of newly synthesized 32 S and 28 S rRNA which had no counterpart 18 S molecules. The extent of the 18 S deficiency was estimated from methylation studies, and was found to be about 50%. Thus, in resting lymphocytes, about half of the 18 S rRNA molecules originally synthesized are lost, presumably through degradation, if the model for rRNA production outlined above is correct. The apparent wastage of 18 S rRNA was reduced or eliminated after the lymphocytes were stimulated to grow. It is proposed that the wastage of rRNA in resting lymphocytes is part of a control mechanism which regulates lymphocyte growth by limiting the accumulation of ribosomes.