Activation of double-stranded RNA dependent protein kinase by ribosomal RNA precursors.

Two major changes in RNA metabolism occured in macrophages expressing tumoricidal activity: a down regulation of total RNA synthesis and an imbalanced accumulation of ribosomal RNA precursors with double stranded secondary structure. The aim of this study was to investigate a possible role of endogenous ds rRNA precursors in the activation of the dsRNA dependent protein kinase. Using a cell free transcription system purified rRNA precursors were obtained from the murine rRNA gene. The results indicate that rRNA precursors are potent activators of the dsPK. The effects are dose dependent and are not affected by treatment of rRNA precursors with proteinase K or RNase A. The treatment with RNase V(1), specific for dsRNA, completely abrogates the activity of transcripts. The results suggest that endogenous RNA, namely rRNA, could control dsPK activation and it can be speculated that dsPK activation may be involved in the control of tumoricidal activity by macrophages.