INHIBITION OF RIBONUCLEASE-P ACTIVITY BY RETINOIDS

The effect of two naturally occurring (retinol and all-trans retinoic acid) and two synthetic (isotretinoin and acitretin) analogs of vitami n A (retinoids) on tRNA biogenesis was investigated employing the RNas e P of Dictyostelium discoideum as an in vitro experimental system. RN ase P is an ubiquitous and essential enzyme that endonucleolytically c leaves all tRNA precursors to produce the mature 5' end. All retinoids tested revealed a dose-dependent inhibition of RNase P activity, indi cating that these compounds may have a direct effect on tRNA biogenesi s, Detailed kinetic analysis showed that all retinoids behave as class ical competitive inhibitors. The K-i values determined were 1475 mu M for retinol, 15 mu M for ah-trans retinoic acid, 20 mu M for isotretin oin, and 8.0 mu M for acitretin, On the basis of these values acitreti n is a 184, 2.5, and 1.9 times more potent inhibitor, as compared with retinol, isotretinoin, and all-trans retinoic acid, respectively. Tak ing into account that retinoids share no structural similarities to pr ecursor tRNA, it is suggested that their kinetic behavior reflects all osteric interactions of these compounds with hydrophobic site(s) of D, discoideum RNase P.