Glucocorticoids modify the rate of ribosomal RNA synthesis in rat thymus cells by regulating the polymerase elongation rate.
The mechanism by which glucocorticoids inhibit RNA polymerase A activity, and hence rRNA synthesis, in rat thymus cells has been investigated. Studies of the intranuclear distribution of RNA polymerase A between chromatin bound ("engaged") and unbound ("free") forms revealed that the steroid-mediated inhibition of the activity of the "engaged" form of the enzyme was not accompanied by significant changes in "free" pool activity. In the presence of rifamycin AF/0-13, an inhibitor of re-initiation of RNA polymerase A, the rate of [3H]UMP incorporation into RNA was slower in nuclei from steroid-treated cells than in those from control cells, although in both conditions similar plateau levels of UMP incorporation were attained. Direct measurements of the numbers of transcribing RNA polymerase A molecules and of elongation rates showed that the inhibition of pre-rRNA synthesis was the result of a decrease in enzyme elongation rate; no significant change was observed in the number of transcribing enzymes. The steroid-induced inhibition of pre-rRNA synthesis was selectively abolished by mild proteolysis of nuclei, suggesting the involvement of a labile, regulatory glucocorticoid-induced protein. It is concluded that glucocorticoid treatment of rat thymus cells decreases 45S rRNA synthesis primarily by decreasing the polyribonucleotide elongation rate of RNA polymerase A, possibly by modification of the enzyme.
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008297:Male; D012318:RNA Polymerase I / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012294:Rifamycins / Q000494:pharmacology; D013950:Thymus Gland / Q000201:enzymology*; D014158:Transcription, Genetic; D014357:Trypsin / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism
D005938:Glucocorticoids; D012335:RNA, Ribosomal; D012294:Rifamycins; C006019:AF 013; D003907:Dexamethasone; D006160:Guanosine Triphosphate; D012318:RNA Polymerase I; D014357:Trypsin; D014544:Uridine Triphosphate