Studies on the Role of Uncharged tRNA in Pleiotypic. Response of Animal Cells

Abstract

Experiments were carried out to assess the physiological significance of the charging level of tRNA. Histidinol, a competitive inhibitor of charging of histidinyl tRNA (tRNAHis), was used to induce uncharged tRNA in mammalian cells [Ehrlich ascites cells and mouse embryo 3T6 fibroblasts]. Both in the presence of histidinol and under histidine depletion, about 40% of the tRNAHis is uncharged. Concomitant with this appearance of uncharged tRNA the pools of GTP and ATP are decreased rapidly by 25-30%. The synthesis of both protein and ribosomal RNA is inhibited, whereas that of nucleoplasmic RNA is not affected; the uptake of 2-deoxyglucose, phosphate, Ca2+, uridine and adenosine is inhibited, and the growth of 3T6 fibroblasts is arrested. The appearence of uncharged tRNA is possibly one of the earliest events occurring under conditions of amino acid starvation, which in turn causes the various metabolic changes observed.