Biomedical subjects

F Grummt

Publications and source records attributed to F Grummt.

68 records · Page 4Linked to original sources

PubMed1976

Studies on the role of uncharged tRNA in pleiotypic response of animal cells.

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

Animals↗

PubMed1976

Amino acid starvation affects the initiation frequency of nucleolar RNA polymerase.

The synthesis of ribosomal precursor RNA in mouse ascites nucleoli derived from cells starved for amino acids is compared with the activity of nucleoli from control cells cultivated in the presence of all amino acids. It is shown that deprivation of a single essential amino acid from the culture medium results in a drastic decrease of the RNA-forming capacity of the isolated nucleoli by a factor of 2-3. This switchoff in rRNA synthesis is a very fast process. Half-maximal inactivation occurs after only 30 min. Addition of amino acids to starved cells leads to a rapid recovery, which is reflected by a sharp increase in the RNA polymerase activity of the isolated nucleoli. Studies on the molecular mechanism of this amino acid-mediated control of rRNA synthesis indicate that this effect is not caused by different growth rates of the RNA chains, but rather by an altered initiation frequency of the RNA polymerase in vivo. Whereas in nucleoli derived from cells grown in full medium almost all the polymerase is tightly bound in a transcriptional complex, a high amount of "free" polymerase which becomes active after addition of exogenous template is present in nucleoli from starved cells.

Cell Division↗

PubMed1976

Control of nucleolar RNA synthesis by the intracellular pool sizes of ATP and GTP.

The influence of amino acid starvation on both the pool sizes of nucleoside triphosphates and the rRNA synthetic capacity of Ehrlich ascites cells was studied. The results indicate that under shiftdown conditions, an immediate shrinkage of the cellular ATP and GTP levels occurs. Concomitant with this, protein and rRNA syntheisis are markedly inhibited. If the pool sizes of purine nucleaside triphosphates are expanded by adding adenosine or guanosine to cells cultured in histidine-free medium, the nucleolar RNA synthesis is fully restored, while protein synthesis remains inhibited. The results suggest that the rate of pre-rRNA transcription may be controlled by the actual nucleoside triphosphate levels of the cells rather than by short-lived protein(s), as has been previously postulated.

Adenosine Triphosphate↗

PubMed1974