Chymotrypsin treatment of glucocorticoid receptor attenuates RNA-dependent inhibition of DNA binding. Evidence for a distinct RNA-binding site.

Certain types of RNA can prevent the association of the rat liver glucocorticoid receptor with DNA. This inhibition of receptor binding to DNA cannot be mitigated by increasing amounts of DNA, suggesting that the RNA is not merely acting as a competitive inhibitor. Treatment of partially purified receptor with low concentrations of chymotrypsin eliminates the inhibitory effects of some RNAs without negatively affecting the DNA-binding ability of the receptor. Potent inhibitors of the receptor-DNA association, such as poly(G) and poly(X), still inhibit DNA binding of the treated receptor, although to a lesser extent than the untreated controls. However, moderate inhibitors, such as tRNA and poly(U), no longer inhibit the receptor-DNA association at low concentrations. We take these findings to suggest that RNA inhibition of DNA binding is due to the interaction of the RNA at a distinct RNA-binding site. This site may serve as a regulator site for the receptor-DNA association.