Modulation of ribonuclease P activity by calcipotriol.
The effects of cholesterol, 7-dehydrocholesterol, vitamin D3 and several synthetic vitamin D3 analogs on ribonuclease P (RNase P) were investigated using a cell-free system from the slime mold Dictyostelium discoideum. RNase P is an ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5' end. Among the compounds tested, only calcipotriol was capable of affecting RNase P activity, and revealed a bimodal action at the kinetic phase of the reaction. Depending on the concentration of the drug, both activation and inhibition of tRNA maturation were observed, indicating that calcipotriol may have a direct effect on tRNA biogenesis, possibly associated with the presence of a highly reactive small ring on the side chain of its molecule.
Papadimou
E
E
Department of Biochemistry, School of Medicine, University of Patras, Greece.
Monastirli
A
A
Stathopoulos
C
C
Tsambaos
D
D
Drainas
D
D
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D003684:Dehydrocholesterols / Q000737:chemistry / Q000494:pharmacology; D004023:Dictyostelium / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D043262:Ribonuclease P; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013329:Structure-Activity Relationship
D003684:Dehydrocholesterols; D016337:RNA, Catalytic; C055085:calcipotriene; D002762:Cholecalciferol; D012343:RNA, Transfer; D002784:Cholesterol; C016705:7-dehydrocholesterol; D004722:Endoribonucleases; D043262:Ribonuclease P; D012259:Ribonuclease, Pancreatic; D002117:Calcitriol