The induction of Alu-sequence transcripts by glucocorticoid in rat liver cells

Two cDNA clones isolated from a library prepared from dexamethasone-treated rat hepatoma cells have permitted us to detect the presence and the induction of heterogeneous, mainly short, RNA molecules in hepatoma cells and in rat liver, but not in several other rat tissues. The induction by dexamethasone is inhibited by 100 X progesterone. Pulse label experiments suggest that it occurs in part at least, at the level of transcription and may be mediated by RNA polymerase III. The induction of the RNAs is stimulated by cycloheximide, even in the absence of hormone, but not significantly by other stressful conditions. One line of hepatoma cells spontaneously lost its ability to induce these RNAs and synthesized them constitutively. These altered cells showed proper induction of another dexamethasone-mediated response, indicating that the glucocorticoid receptor was functionally normal in these cells. The two clones contain a type 2 Alu-like sequence. The short RNAs can be distinguished from 7SL RNA, which also contains Alu-sequences. We hypothesize that the synthesis of these RNAs may be regulated by an inhibitor of transcription which is inactivated by dexamethasone. Accordingly, cycloheximide relieves the inhibition by preventing synthesis of the inhibitor and the altered cell line has spontaneously lost the function of the inhibitor. The function of these RNAs for the cell is not known. We believe this to be the first report of hormone-regulated tissue specific synthesis of repeat-sequence transcripts.